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## 2015.03.10
08:50:19 -04'00'

JAMES HETRICK Digitally signed by JAMES HETRICK DN: c=US, o=U.S. Government, ou=USEPA, ou=Staff, cn=JAMES HETRICK, dnQualifier=0000005599
Date: 2015.03.10 16:35:20 -04'00'

ROSANNA LOUIEJUZWIAK
2015.03.11 08:18:50
-04'00'

### Page 2 of 62

estuarine/marine invertebrate studies, freshwater f ish studies, aquatic (vascular and nonvascular) plant and terrestrial plant studies.

Additional fate and transport studies are not being requested for myclobutanil because a reasonably conservative risk assessment can be cond ucted with existing data gaps; however, additional fate data could assist in refining the a ssessment.

Many of the myclobutanil product labels do not spec ify the maximum number of applications that can be applied per year or crop cycle and/or t he number of crop cycles per year. Some labels are missing a single maximum application rat e. We request that in completing the Use Summary Table, the registrants provide this informa tion.

INTRODUCTION

Myclobutanil is a systemic fungicide used to contro l powdery mildew on a number of crops. It is a triazole fungicide in the conazole class of fungi cides. Myclobutanil is classified as a sterol biosynthesis inhibitor (SBI) and is further classif ied as a demethylation inhibitor (DMI) fungicide because it inhibits the enzyme sterol 14-demethylas e, which disrupts the ergosterol biosynthesis pathway that is vital to fungal cell w all structure and function (FRAC 2012, Roberts and Hutson 1999). Myclobutanil is a Group 3 Fungici de.

Myclobutanil was first registered in the United Sta tes in 1984. Based on the Summary Level Usage Analysis (SLUA) report, between 2004 -2012, t he agricultural use with the highest usage (in pounds a.i. applied per year) is grapes with 50 ,000 average pounds used. The next highest usage crops were apples (20,000 average pounds per year) then almonds, tomatoes, and cherries with 8,000, 7,000, and 5,000 pounds used p er year, respectively. Usage data are currently not available for the non-agricultural us es of myclobutanil.

All current labeled uses of myclobutanil include the fo llowing food uses: almond, apple, apricot, artichoke, asparagus, beans (succulent), blackberry , boysenberry, caneberries, canistel, carrot (including tops), cherry, chrysanthemum garland, co tton, cucurbits (pumpkin, squash, watermelon), currant, eggplant, gooseberry, grapes, hops, lettuce (head, leaf), loganberry, mamey (mammee apple), mango, mayhaw (Hawthorn), min t/peppermint/spearmint, nectarines, okra, olallie berries, papaya, peach, p epper, pimento, plum, prune, raspberry (black, red), sapodilla, sapote white, soybeans (unspecifie d), star apple, strawberry, subtropical/tropical fruit and tomato. Non-food/non-feed uses include b luegrass, commercial/industrial lawns, cotton (seed), Douglas Fir (seed orchard, shelter b elt), golf course turf, grasses grown for seed, household/domestic dwellings (outdoor premises), hy brid cottonwood/poplar plantations, loblolly pine (forest), ornamental and shade trees, ornamentals (herbaceous plants, lawns and turf, sod farm (turf), unspecified, woody shrubs an d vines), residential lawns and slash pine forest (USEPA 2014 a.).

Application types include broadcast (aerial and gro und), chemigation, directed spray, foliar treatment, ground spray, high volume spray (dilute) , low volume spray (concentrate), seed treatment, spot treatment, and spray (USEPA 2014 a. ).

Based on current labels, the maximum single applica tion rate ranges from 0.1037 to 1.4 pounds of active ingredient per acre (lb a.i./acre) and up to 16 applications per year for some uses. The

### Page 3 of 62

highest annual application rates generally are foun d in the ornamentals (sod farms, lawns and turf) and residential lawns. However, the number of applications of myclobutanil that can be applied per calendar year or the maximum annual app lication rate for a given use is not explicitly stated on many of the current labels.

The chemical profile produced by BEAD, located in t he docket, lists the use patterns of maximum exposures for the current uses of Myclobuta nil. EFED will use application scenarios that result in maximum exposure scenarios for a giv en use for the risk assessment. Any absence of information on the labels that specifies the max imum single application rate, the application interval, the annual maximum rate allowed (lb a.i./ year), or application method may result in conservative assumptions.

Previous Ecological Assessments

Myclobutanil has been assessed a number of times fo r new uses including Section 18 assessments since the original registration in 1984 . Such assessments include a 2009 California Red-Legged Frog Endangered Species Assessment and S ection 3 Ecological Risk Assessment for Myclobutanil (October 12, 2007) (DP336613). EFED ev aluated these assessments and others for myclobutanil in association with the current toxici ty, exposure, and use information to
determine if sufficient data are available and if f urther updates are needed to support registration review. In some of the previous assess ments, risks were assessed using the parent compound only, whereas others took into considerati on degradates of concern using the total toxic residue (TTR) approach. In the most recent a ssessment conducted in 2012, stressors of concern for aquatic organisms were considered to be myclobutanil and 1,2,4-triazole, while stressors of concern for terrestrial organisms were considered to be myclobutanil, the plant metabolite RH-9090, 1,2,4-triazole, and triazole co njugates 1,2,4-triazole alanine and 1,2,4 triazole acetic acid (also referred to as triazole alanine and triazole acetic acid) (D402503). Based on the review of available toxicity data and the EC OSAR results considered in the development of this Problem Formulation, the aquatic risk asses sment conducted for registration review will likely consider only the parent compound, while the approach to terrestrial risk will remain the

same.

Based on the various past assessments which spanned a range of application rates and patterns, risk tended to be greatest for freshwater fish (acu te), marine/estuarine invertebrates (acute), birds (acute and chronic), and mammals (acute and c hronic) depending on the use patterns and application rates. At the time of many of these as sessments, certain toxicity data were not available [e.g. terrestrial plants, aquatic vascula r plants, chronic avian, chronic invertebrates (freshwater and marine/estuarine) or acute marine/e stuarine fish, terrestrial invertebrates] so risk was not assessed quantitatively or was presume d in the absence of data. A qualitative summary of previous risk concerns identified is pro vided in Table 2.

### Page 4 of 62

Table 2. Summary of Previous Risk Concerns Identifi ed for Myclobutanil a

Exposure
Basis Birds Mammals Terrestrial
Plants Terr.

Inverts. (honey
bee hazard) Fish Aquatic

Inverts Aquatic

Plants Ground

Water Persistence Degradates
of Concern

Acute Yes Yes Yes b No No Yes c Yes b No Yes Yes Chronic Yes Yes No No

a. At least one LOC has been exceeded in previous asse ssments b. Based on lack of toxicity data, risks were assumed

c. Estuarine/marine invertebrates only



### Previous Drinking Water Assessments

The most recent drinking water assessment (DWA) for myclobutanil was conducted in 2012, which re-assessed the use with the highest applicat ion rate, turf (USEPA, 2012 a.). The surface water estimated drinking water concentrations (EDWC s) for myclobutanil were calculated using a Tier II model (PRZM-EXAMS) and took into account additional aerobic aquatic metabolism data and revised percent crop area guidance (USEPA, 2012 b.). The estimated groundwater concentrations of myclobutanil were calculated usin g PRZM-GW. The groundwater EDWCs were lower than the surface water EDWCs, and EFED r ecommended using the surface water EDWCs for human health (dietary) risk assessment. T he maximum concentrations of myclobutanil in surface water were estimated to be 218 μg/L for the 1-in-10-year annual peak, 172 μg/L for the 1-in-10-year annual average, and 1 17 μg/L for the 30 year annual average. The maximum peak concentration of myclobutanil in groun dwater was estimated to be 41.5 μg/L.

The most recent EDWCs for 1,2,4-triazole, 1,2,4-tri azole alanine, and 1,2,4-triazole acetic acid were calculated in support of the 2006 aggregate as sessment for triazole-derivative fungicides (USEPA, 2006 a.; USEPA, 2006 b.). The highest 1,2, 4-triazole, 1,2,4-triazole alanine, and 1,2,4-
triazole acetic acid EDWCs calculated in this asses sment were for the myclobutanil turf use, which resulted in the surface water EDWCs (using PR ZM-EXAMS) shown in Table 3. A groundwater EDWC of 1.06 μg/L was calculated for 1, 2,4-triazole using SCI-GROW. More details on the methods and assumptions used to calculate th ese EDWCs may be found in the aggregate

assessment.

Table 3. Surface Water EDWCs for 1,2,4-Triazole an d its Conjugates of Concern from Use of Myclobutanil on Turf a 

### (D320682)

Myclobutanil Degradate Estimated Surface Water Drinking Water Concentratio ns (μg/L) 1-in-10-year annual peak 1-in-10-year
annual mean 36-year
annual mean 1,2,4-Triazole a 41.0 11.0 2.69 1,2,4-Triazole Acetic Acid (TAA) b 75.4 20.2 4.95

1,2,4-Triazole Alanine (TA) c 92.7 24.9 6.08

### Page 5 of 62 a Golf Course Turf PA golf course turf scenario; app lication rate based upon 6 applications of myclobut anil at 1.73 lb a.i./A; 10.38 lb a.i./A/yr. 1,2,4-Triaz ole application was obtained from molecular weight conversion times myclobutanil application rate time s max percent formation rate for triadimefon (turf = (69.0/288.78)*1.73*0.307), as this was believed to be the maximum percent formation rate for all fungicides in the conazole class.

b TAA = (127.10/69.0)*1,2,4-Triazole concentration.

c TA = (156.15/69.0)*1,2,4-Triazole concentration.



### Clean Water Act Programs

Myclobutanil is not identified as a cause of impair ment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. Total Maximum Daily Load (TMDL) criteria have not been developed for myclobutanil ( http://iaspub.epa.gov/tmdl_waters10/attains_impaire d_waters.tmdls?p_pollutant_group_id=8

85 ). Aquatic benchmarks have been established for myclob utanil for freshwater fish (acute 1,200 μg/L, chronic 980 μg/L), freshwater invertebr ates (acute 5,500 μg/L), and freshwater nonvascular plants (acute 830 μg/L) ( http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_li fe_benchmark.htm ). Any data submitted or otherwise located as part of the regis tration review process may be used to revise or establish new aquatic life benchmarks, if applic able.

1. ENVIRONMENTAL FATE AND TRANSPORT

Physical and Chemical Properties of Myclobutanil

Selected physicochemical properties of myclobutanil are shown in Table 4 . Based on these properties alone, volatility is not expected to be a major dissipation pathway for myclobutanil, and myclobutanil is not expected to bioaccumulate.

Table 4. Selected Physical/Chemical Parameters of M yclobutanil

Chemical name Property Data Source (MRID) Molecular weight 288.775 g/mol
-



### Aqueous Solubility 142 mg/L at 25 ° C 00141683
48951203 Milli-RO Water: 118 mg/L at 20 ° C pH 4.0 buffer: 115 mg/L at 20 ° C pH 7.0 buffer: 107 mg/L at 20 ° C pH 9.0 buffer: 115 mg/L at 20 ° C 46802501

Vapor Pressure 1.60 × 10 -6 

### torr at 25 ° C 48951203

< 9.75 × 10 -6 

### torr at 25 ° C 46802501 Henry’s Law Constant 3.25 x 10 -09 

### atm m 3 

### /mole at 25 ° C Calculated

Octanol-water partition coefficient (log Kow) 2.47 at 22 ° C 00162541

2.84

- 2.98 at unspecified ambient temperature

Mean: 2.94 00141683

### Page 6 of 62

Environmental Fate and Transport of Myclobutanil

Table 5 summarizes the environmental fate properties of my clobutanil, while Appendix A provides the chemical structure of myclobutanil and its major degradation product, 1,2,4- triazole. Due to its persistence and mobility, myc lobutanil applications may lead to surface water contamination through spray drift, runoff, se diment erosion and groundwater contamination through leaching. Myclobutanil has b een detected in rain in several agricultural watersheds in California (Vogel et al. 2008); thus, there is also a potential for atmospheric
transport.

Myclobutanil degrades rapidly as a result of aqueou s photolysis (4 day half-life) and is relatively stable to soil photolysis (144 day half-life). Mycl obutanil is stable to hydrolysis. The only aerobic soil metabolism study available for myclobutanil in dicates that the pesticide undergoes nonlinear microbial degradation in aerobic soil, with a Double First-Order in Parallel (DFOP) half-life of 750 days. Myclobutanil appears to slowly degrad e in a linear fashion in aerobic aquatic environments (half-lives of 416 and 834) and is ver y persistent anaerobic aquatic environments. The wide range of half-lives in terrestrial field s tudies indicates that myclobutanil may dissipate rapidly or slowly depending on the environmental co nditions.

Myclobutanil has the potential to leach into ground water, as it is classified as moderately mobile (K foc 

### = 226 – 923) (FAO 2000). A leaching study conducte d on one soil suggests that myclobutanil residues will remain primarily in the top 10 cm of soil, although residues were found at the 20 inch (maximum) depth and in leachate (MRID 00141681 ). The adsorption/desorption study results indicate that soil sorption of myclobutanil is highly influenced by soil acidity and soil cation exchange capacity. A regression analysis ind icated that lower soil acidity results in increased soil sorption of myclobutanil; an increas e in the pH by 1 increases the K f

### by 3 (rsquared = 0.81; p-value < 0.05). Similarly, an incr ease of soil cation exchange capacity of 1 meq/100g results in an increase in the K f 

### of 0.7 (r-squared = 0.81; p-value < 0.05). Sorption may also be influenced by soil organic carbon content. The coefficient of variance is lower for the

K foc 

### ’s than for the K f 

### ’s, indicating a correlation between myclobutanil s oil sorption and soil organic carbon content; however, a regression analy sis of percent organic carbon versus K f 

### for the five soils did not find this relationship to be statistically significant.

Table 5. Chemical Properties and Environmental Fate Parameters of Myclobutanil

Parameter Value* Description Source (MRID) Study Status

Persistence

Hydrolysis halflife Stable pH 5, 7, 9 at
22 ± 2.3°C 00141679 Acceptable

Aqueousphotolysis halflife 4 days

(IORE) Study conducted at 31°C 00164560

40641501

40319801

40528801 Studies acceptable only in

combination, not individually

### Page 7 of 62 Parameter Value* Description Source (MRID) Study Status

Soil photolysis
half-life 144

days (SFO) Lawrenceville silt loam

pH 5.3 at 34°C 00164987
00164988 Studies acceptable only in

combination, not individually

Aerobic soil
metabolism halflife 750

days (DFOP) Lawrenceville silt loam

pH 5.3 00141680

00164561 Individual study acceptable

Anaerobic soil
metabolism halflife Stable Lawrenceville silt loam flooded after 30 days under aerobic
conditions
Flood water not characterized 00141680

00164561 Individual study acceptable

Aerobic aquatic
metabolism halflife (total system) Rhine

River

416 days (SFO)

Pond

834 days (SFO) Rhine River

pH 7.36-8.53
at 17.1°C

Pond pH 7.46-8.40
at 12.8°C 47454401 Acceptable

Mobility

Adsorption– K f 4.47

1 / n = 0.89 Hagerstown Clay Loam: 1.98% OC, soil pH 6.4, CEC 9.4 meq/100g

00141682 Supplemental 1.46

1 / n = 0.89 Lakeland Agricultural Sand: 0.55% OC, soil pH 5, CEC 1.7 meq/100g

7.10

1 / n = 0.88 Lawrenceville Silty Loam: 1.19%

OC, soil pH 6.1, CEC 11.9 meq/100g

9.81

1 / n = 0.85 Pasquotank Sandy Loam: 1.68%

OC, soil pH 7.2, CEC 12.5 meq/100g

2.40

1 / n = 0.91 Cecil Clay: 0.26% OC, soil pH 4.7,

CEC 6.9 meq/100g

5.05 MEAN Study conducted at “ambient”
temperature

Adsorption– K foc 226 Hagerstown Clay Loam: 1.98% OC, soil pH 6.4, CEC 9.4 meq/100g

266 Lakeland Agricultural Sand: 0.55% OC, soil pH 5, CEC 1.7 meq/100g

### Page 8 of 62 Parameter Value* Description Source (MRID) Study Status

596 Lawrenceville Silty Loam: 1.19%

OC, soil pH 6.1, CEC 11.9 meq/100g

584 Pasquotank Sandy Loam: 1.68%

OC, soil pH 7.2, CEC 12.5 meq/100g

923 Cecil Clay: 0.26% OC, soil pH 4.7,

CEC 6.9 meq/100g

519.04 MEAN

Study conducted at “ambient”
temperature

Field Dissipation

Terrestrial FieldDissipation HalfLife 9.36

days (IORE) Winter wheat - Newtown,

Pennsylvania Silty Loam, 0-3” depth (leached to deepest sampling depth of 6-12”) 00164563
00164987

Acceptable

80.7 days (SFO) Winter wheat - Cleveland,

Mississippi Loam, 0-3” depth (leached to deepest sampling depth of 6-12”)

409 days (SFO) Bare ground - Fresno County, California Sandy Loam (leached to deepest sampling depth of 18-

24”) 42181101 Acceptable

243 days (IORE) Bare ground - Santa Clara County,

California Loam (leached to deepest sampling depth of 18-

24”)

81.6

days** (DFOP) Turf – Baptistown, New Jersey Silt

Loam (leached to deepest sampling depth of 18-24”) 43087904 Supplemental

*All values have been re-estimated by the authors o f this document. Representative half-lives are estimated SFO half-lives (for EFED modeling inputs) from a degradation curve that does not necessarily follow the SFO equation. Representative half-life v alues were calculated using nonlinear regression an d SFO, DFOP, or IORE equations. The equations can be found in the document, Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half-life Values and Characterizing Pesticide Degradation (US EPA 2012). Representative half-life values calculated in this table do not i nclude
unextracted residues. **Representative half-life calculated from post-tre atment day 10 to the end of the study, as maximum myclobutanil concentrations were observed on day 10

.

### Page 9 of 62

Transformation Products

Myclobutanil degrades to 1,2,4-triazole when subjec ted to light in aquatic environments or exposed to microbes in aerobic soil. In the aqueou s photolysis study, 1,2,4-triazole comprised 49% of the applied radioactivity on day 30 of the s tudy. In the aerobic soil metabolism study, 1,2,4-triazole comprised 18% of the applied radioac tivity on days 150 and 180 of the study, declining to 13% at the end of the study (day 367). 1,2,4-triazole was observed at all depths in the terrestrial field dissipation studies and its f ormation ranged from 2.1% (6-12” segment) to 58.6% (3-6” segment). 1,2,4-triazole is the only ma jor transformation product of myclobutanil observed in field and laboratory studies; however, the analytical methods used in those studies are rarely able to identify 1,2,4-triazole conjugat e residues separately from 1,2,4-triazole. Appendix A provides additional detail on degradation of myclo butanil to 1,2,4-triazole in the environment, including degradate and conjugate stru ctures.

Based on registrant-submitted laboratory and field studies, 1,2,4-triazole is persistent (average aerobic half-life = 645 days) and very mobile (K f 

### ’s 0.23 – 0.84) in the soil. 1,2,4-triazole’s major routes of dissipation are leaching into groundwater and runoff into surface water.

Hydrolysis, aqueous photolysis, and soil metabolism are not major routes of 1,2,4-triazole degradation (hydrolysis half-lives 99 - 421 days; s table to aqueous photolysis). Microbial degradation of 1,2,4-triazole in aerobic soils is h ighly varied (half-lives from 20 days to stable) and consistently non-linear. The high variability in the half-lives may be explained, in part, by the application rate used in the aerobic soil metab olism studies; higher levels of application (1 to 50 ppm in soil) seem to suppress microbial degradat ion. On average, even with this variability, 1,2,4-triazole is persistent in aerobic soil. The average aerobic soil metabolism half-life for treatment levels at or less than 1 ppm is 197 days, while the average half-life incorporating treatment levels up to 50 ppm is 645 days. 1,2,4-tr iazole is moderately persistent in anaerobic soil (half-life 81 days).

1,2,4-triazole’s major transformation products are the conjugate 1,2,4-triazole acetic acid and hydroxytriazole. Both transformation products are formed through microbial degradation in
aerobic soils. In one aerobic soil metabolism stud y 1,2,4-triazole acetic acid comprised a maximum of 18% of the applied radioactivity (day 98 ), declining to 11.7% by the end of the study (day 293). In a separate aerobic soil metabo lism study, hydroxytriazole comprised a maximum of 30.8% of the applied radioactivity (day 12), declining to 0.6% at the end of the study (day 180). 1,2,4-triazole acetic acid is also formed through anaerobic soil metabolism, and was observed at 50% of applied radioactivity on the last sample day of the only anaerobic soil metabolism study available for 1,2,4-triazole. 1,2 ,4-triazole alanine was also detected as a minor transformation product in the anaerobic soil metabolism study.

1,2,4-triazole has the potential to leach into grou ndwater, as it is classified as mobile to moderately mobile (K foc 

### = 48 - 202) (FAO 2000). Leaching studies conducted for 1,2,4-triazole suggest that the compound and its transformation pr oducts are mobile in a variety of soil types, with radiolabelled residues leaching to the maximum soil depth considered, 30 centimeters (MRIDs 00133372 and 45284030).

Field dissipation studies indicate that 1,2,4-triaz ole has the propensity to leach, as the compound was detected up to 12 inches soil depth in field plots. Adsorption/desorption study

### Page 10 of 62

results indicate that soil organic carbon content a nd CEC do not influence soil sorption of 1,2,4- triazole. Although there is a statistically signif icant positive relationship between K f 

### and soil pH, an increase in soil pH of 1 only increases the K f 

### by 0.15 (r-squared = 0.76, p-value < 0.05).

Table 6 summarizes the environmental fate properties of 1, 2,4-triazole and 1,2,4-triazole acetic acid, while Appendix A provides additional detail on formation of 1,2,4-t riazole transformation products in the environment, including degradate an d conjugate structures.

### Page 11 of 62

Table 6. Chemical Properties and Environmental Fate Parameters of 1,2,4-Triazole and Conjugates

Parameter Value* Description Source (MRID) Study Status

1,2,4-Triazole

Persistence

Hydrolysis
half-life 303 days

(DFOP) pH 5 acetate buffer at 25°C

00133373 Supplemental 421 days (DFOP) pH 7 phosphate buffer at 25°C

98.7 days (SFO) pH 9 borate buffer at 25°C

Aqueous photolysis
half-life Stable pH 7 distilled water temperature not reported 45284026 Supplemental

Aerobic soil
metabolism
half-life 378 days

(DFOP) Les Barges (Swiss) silty loam 1 ppm applied pH 7.6 at 25°C 45284027 Supplemental

70.1 days (IORE) Laacher Hof AXXa (German) sandy loam ~0.06 ppm applied pH 6.9 (H2O) at 20±2°C

45284032 Supplemental 319 days (DFOP) BBA 2.2 (German) loamy sand ~0.06 ppm applied pH 6.19 (H2O) at 20±2°C

20.3 (IORE) Laacher Hof A III (German) silt loam ~0.06 ppm applied pH 7.88 (H2O) at 20±2°C

Stable(DFOP halflife 1,530 days) Standard Soil 2.2 50 ppm applied pH 6.0 at 22±2°C
45297203 Supplemental Stable(DFOP halflife 1,550 days) Standard Soil 2.3 50 ppm applied pH 5.5 at 22±2°C

Anaerobic
soil
metabolism
half-life 81.2 days

(SFO) Les Barges (Swiss) silt loam pH 7.31 at 20±2°C 45930701 Acceptable

Mobility

Adsorption

– K f 0.84

1 / n = 0.90 Alpaugh Silty Clay: 0.65% OC, soil pH 8.8, CEC 30.5 meq/100g

40891501 Acceptable 0.27

1 / n = 0.63 Hollister Clay Loam: 1.74% OC, soil pH 6.9, CEC 16.9 meq/100g

0.23

1 / n = 0.89 Lakeland Sand: 0.12% OC, soil pH 4.8, CEC 1.2 meq/100g

### Page 12 of 62 Parameter Value* Description Source (MRID) Study Status

1,2,4-Triazole

0.73

1 / n = 0.92 Lawrenceville Silty Clay Loam: 0.70% OC, soil pH 7, CEC 6.6 meq/100g

0.72

1 / n = 1.02 Pachappa Sandy Loam: 0.81% OC, soil pH 6.9, CEC 11.1 meq/100g

0.56 MEAN

Study conducted at 25±1°C

Adsorption

– K foc 129 Alpaugh Silty Clay: 0.65% OC, soil pH 8.8, CEC 30.5 meq/100g

48 Hollister Clay Loam: 1.74% OC, soil pH 6.9,

CEC 16.9 meq/100g

202 Lakeland Sand: 0.12% OC, soil pH 4.8, CEC 1.2 meq/100g

104 Lawrenceville Silty Clay Loam: 0.70% OC, soil pH 7, CEC 6.6 meq/100g

89 Pachappa Sandy Loam: 0.81% OC, soil pH 6.9,

CEC 11.1 meq/100g

114 MEAN

Study conducted at 25±1°C

Field Dissipation

Terrestrial
Field Dissipation
Half-Life 445 days

(IORE) Newtown, Pennsylvania Silty Loam, 0-3” depth

(leached to 6-12” segment; study sampled to 36”

depth) 45284025 Supplemental

391 days (SFO) Newtown, Pennsylvania Silty Loam, 0-3” depth

(leached to deepest sampling depth of 6-12”) 00164564 Supplemental 525 days (SFO) Cleveland, Mississippi Loam, 0-3” depth

(leached to deepest sampling depth of 6-12”)

1,2,4-Triazole Acetic Acid

Persistence

Aerobic soil
metabolism
half-life 5.01

days** (IORE) SP-2.1 (German) sand pH 5.2 at 20°C

46017601 Pending

Review 6.27 days** (IORE) SP-2.2 (German) loamy sand pH 5.6 at 20°C

7.04 days** (DFOP) SP-2.3 (German) sandy loam pH 6.3 at 20°C

*All values have been re-estimated by the authors o f this document. Representative half-lives are estimated SFO half-lives (for EFED modeling inputs) from a degradation curve that does not necessarily follow the SFO equation. Representative half-life v alues were calculated using nonlinear regression an d SFO, DFOP, or IORE equations. The equations can be found in the document, Standard Operating Procedure for Using the NAFTA Guidance to Calculate Representative Half-life Values and Characterizing

### Page 13 of 62 Pesticide Degradation (US EPA 2012). Representative half-life values calculated in this table do not i nclude
unextracted residues. **This aerobic soil metabolism study did not identi fy any conjugates or degradates of 1,2,4-Triazole A cetic Acid, even though transformation products formed to upwards of 75% applied radioactivity. It is possib le that 1,2,4-Triazole Acetic Acid in combination with its conjugates of concern are persistent in aerobi c soil, even though, based on the data in this study, 1,2,4 -Triazole Acetic Acid is not persistent in aerobic soil.



### 2. RECEPTORS

Tables 7 and 8 provide a summary of the aquatic and terrestrial to xicity data, respectively, and the most sensitive surrogate species tested to char acterize the potential acute and chronic ecological effects of myclobutanil. Table 9 provides information on the most sensitive toxicit y data available for myclobutanil degradates. All ava ilable toxicity data for myclobutanil degradates listed in Appendix D

.

Table 7. Summary of the Most Sensitive Endpoints fr om Aquatic Toxicity Studies for Myclobutanil

Taxonomic Group Study

type Surrogate

Species Toxicity MRID (classification) Acute Toxicity

Classification

Freshwater
fish Acute Bluegill Sunfish ( Lepomis
macrochirus ) 96-hr LC 50 : 2.4 mg a.i./L

NOAEC = 1.5 mg a.i./L LOAEC = 2.7 mg a.i./L based on quiescence, loss of equilibrium
and death. 00144285 (Acceptable) Moderately

toxic

Chronic Fathead

minnow ( Pimephales promelas ) NOAEC= 0.98 mg a.i./L 1

LOAEC = 2.2 mg a.i./L based on a 9.7% reduction in body length. Total mortality at 8.5 mg a.i./L 00164986/ 40409201/

40480401 (Acceptable) N/A

Estuarine/
marine fish Acute Sheepshead

minnow ( Cyprinodon variegatus ) 96-hr LC 50 : 4.7 mg a.i./L

NOAEC = 1.2 mg a.i./L LOAEC = 1.8 mg a.i./L (erratic behavior, darkened pigmentation, lethargy; fish at higher concentration levels also exhibited partial loss of equilibrium and rapid respiration). Mortality was 5% at 3.8 mg a.i./L and 100% at 6.3 mg a.i./L 42747903 (Acceptable) Moderately

toxic

Chronic N/A No Data --- ---

Freshwater
invertebrates Acute Water flea ( Daphnia

magna ) 48-hr EC 50 : 11 mg a.i./L

NOAEC = 3.2 mg a.i./L LOAEC = 5.6 mg a.i./L (settled to the bottom). Mortality was 45% at 10 mg a.i./L and 90% at 18 mg a.i./L 00141678 (Acceptable) Slightly toxic

Chronic Water flea

( Daphnia

magna ) Estimated NOAEC using ACR=

3.9 mg a.i./L 2 No Study N/A

### Page 14 of 62

Taxonomic Group Study

type Surrogate

Species Toxicity MRID (classification) Acute Toxicity

Classification

Estuarine /marine
invertebrates Acute Eastern oyster ( Crassostrea virginica) 96-hr EC 50 : 0.68 mg a.i./L

NOAEC = 0.48 mg a.i./L LOAEC = 0.78 mg a.i./L (shell deposition). Inadequate shell growth in controls may underestimate pesticide related shell growth effects. (Discussed in Section 4. Preliminary Identification of Data Gaps) 42747901 (Supplemental) Highly toxic

Mysid shrimp ( Americamysis
bahia ) 96-hr LC 50 : 0.24 mg a.i./L

NOAEC could not be
determined as effects seen at all dose levels (erratic swimming behavior, darkened pigmentation, lethargy). Mortality observed at lowest test concentration of 0.180 mg a.i./L and above. 42747902 (Acceptable) Highly toxic

Chronic Mysid shrimp

( Americamysis
bahia ) NOAEC: 0.0856 mg a.i./L

LOAEC: >0.0856 mg a.i./L No effects reported at any
level. Water quality issues (a maximum pH of 9.98 was reported at the nominal 20 ug a.i./L treatment level). 47968901 (Supplemental) N/A

Aquatic
Plants Non

vascular Green algae

(Selenastrum capricornutum) 120-hr EC 50 : 0.83 mg a.i./L

NOAEC= 0.56 mg a.i./L based on cell density. 41984801 (Acceptable) N/A

Vascular No Data --- --- ---

1 Acute data for fathead minnow was requested in Tab le 11 below to provide data for determination of

an ACR.

2 Estimated from the mysid acute and chronic toxicity data and the daphnid acute data using the acute to chronic ratio (ACR) [0.24/0.0856 x 11/x; x=3.9]

### Page 15 of 62

Table 8. Summary of the Most Sensitive Endpoints f rom Terrestrial Toxicity Studies for Myclobutanil

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Acute Toxicity

Classification

Birds Acute Bobwhite quail ( Colinus virginianus ) Acute LD 50 : 498 mg a.i./kg-bw

NOAEL: not determined LOAEL= 316 mg/kg (lethargy and anorexia). Mortalities at all dose levels (1, 4, 8, 10 and 10, respectively). Good dose

response. 00144286 (Acceptable) Slightly toxic

Subacute Mallard

( Anas platyrhync
hos ) Subacute dietary LC 50 >4090

mg a.i./kg-diet NOAEC= 1250 mg a.i./kg-diet LOAEC= 2220 mg a.i./kg-diet (anorexia and lethargy). Onebird died at 4090 mg a.i./kgdiet. 00144288 (Acceptable) Slightly toxic

Chronic Bobwhite

quail ( Colinus virginianus ) NOAEC= 256 mg a.i./kg-diet

LOAEC >256 mg a.i./kg-diet
No treatment-related effects at any level. Maximum exposure levels less than the predicted EECs. 43087901 (Supplemental) N/A

Mammals 1 Acute Laboratory

mouse ( Mus
musculus ) LD 50 = 1360 mg a.i./kg bw

Mortality at all dose levels tested. Multiple clinical signs, including ataxia, tremors, loss of righting and others – not dose-related; however, early deaths may have affected reporting. 00165239 (Acceptable) Slightly toxic

Acute Laboratory

rat (Rattus norvegicus) LD 50 = 1600 mg a.i./kg bw (M) 00141662 (Acceptable) Slightly toxic

Chronic Laboratory

rat ( Rattus norvegicus ) NOAEC (NOAEL)= 200 mg

a.i./kg-diet (16 mg/kg bw/day) LOAEC (LOAEL)=1000 mg a.i./kg-diet (80 mg/kg bw/day) -testicular, epididymal and prostatic atrophy in P2 males; slight increase in stillborns, decrease in body weight gain 00149581/

00143766 (Acceptable) N/A

### Page 16 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Acute Toxicity

Classification in pups during lactation in F1 and F2 generations

Terrestrial
Invertebrat

es Acute Honey bee ( Apis mellifera

L .) Contact LD 50

> 100 μg a.i./bee 00144289 (Acceptable) N/A

1 Toxicity data for the oral mouse study was more sen sitive than the rat study (oral mouse dose converts to a rat equivalent dose of 665 mg/kg bw). Rat data was included as this endpoint was used in HED assessments and for comparison to degradate toxicit y data where rat was more sensitive than mouse in acute oral study (see Table 9).



### Table 9. Summary of the Most Sensitive Data for eac h taxa for Myclobutanil Degradates (1,2,4-triazole, triazole alanine and triazole ace tic acid) 1

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

1,2,4-triazole (aquatic toxicity)

Freshwater
fish Acute Rainbow Trout ( Oncorhynchus mykiss ) 96 hr-LC 50 = 498 mg

ai/L
NOAEC = 378 mg ai/L
(mortality) 48474301 (Acceptable) None

Chronic (28 day growth toxicity test) Rainbow trout

( Oncorhynchus mykiss ) LC 50 : > 100 mg/L

NOAEC (growth) ≥ 100 mg/L
NOAEC (sublethal effects) = 3.2 mg/L
LOAEC (sublethal effects) = 10.0 mg/L

Observed sublethal
effects included multiple fish being inactive or displaying abnormally low activity, labored respiration, and lying
inactive on the
bottom of the aquarium in the three highest 45880405 (Supplemental) Supplemental due to

non-guideline study

### Page 17 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

concentrations tested between days
23 and

28.

Freshwater
Invertebrat

es Acute Water flea ( Daphnia

magna ) LC 50 = 900 (730 to

2200, 95% C.I.) mg/L. 00133381 Under Review

Acute Water flea

( Daphnia magna) 48-hr EC 50 > 98.1 mg

ai/L

NOAEC = 98.1 mg ai/L (based on mobility, highest concentration tested) 48453206 (Acceptable) None

Aquatic
Plants -

Non
vascular Acute Freshwater Algae ( Pseudokirchn
eriella subcapitata, formerly
Selenastrum capricornutum ) 96-hr endpoints:

Biomass (most sensitive):

EC 50 = 14 mg ai/L
NOAEC = 3.1 mg ai/L
Cell Density:

EC 50 = 18 mg ai/L
NOAEC = 6.8 mg ai/L

Growth Rate:

EC 50 > 31 mg ai/L
NOAEC = 6.8 mg ai/L 45880401 (Acceptable) None

Acute Green algae ( Scenedesmus subspicatus ) EC 50 = 6.3 (5.5 to 7.1,

95% C.I.) mg/L 00133382 Under Review

1,2,4-triazole (terrestrial toxicity)

Birds Acute Coturnix quail (Coturnix japonica) LD 50 >316 mg/kg bw 45284015 Under Review

Acute Bobwhite quail

( Colinus virginianus ) LD 50 = 770 mg/kg bw

NOAEL = 245 mg/kg
bw

LOAEL = 392 based on reduced body weight and food consumption; other
observed effects included mortality 49380701 (Acceptable) None

### Page 18 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments and clinical signs of toxicity

Mammals Acute Laboratory

mouse (Mus musculus) LD 50 = 3650 mg/kg 45284001 Review not available 2

Acute Laboratory Rat

(M)
(Rattus norvegicus) LD 50 = 1375 mg/kg

LD 50 = 1648-3080 mg/kg 45284008

45284004,

45284001 Reviews not

available 2

Reproduction and fertility
effects 0, 250, 500, 3000 ppm M: 15, 31, 189
mkd

F: 18, 36, 218
mkd Laboratory rat

(Rattus norvegicus) Parental:

NOAEC/NOAEL <250 ppm/15 mg/kg/day LOAEC/LOAEL= 250 ppm/15 mg/kg/day
based on decrease in bodyweight, bodyweight gain and spleen weight.

Offspring: NOAEC/NOAEL= <250 ppm/19 mg/kg/day LOAEC/LOAEL= 250 ppm/19 mg/kg/day
based on decrease in bodyweight, bodyweight gain, brain and spleen weights

Reproduction: NOAEC/NOAEL= 250 ppm/15 mg/kg/day Repro LOAEC/LOAEL= 500 ppm/31 mg/kg/day based on abnormal sperm and ↓ # of corpus luteum (CL) in F 1 females
At 3000 ppm/218 mg/kg/day, reproductive failure (no viable offspring), ↑ CL in F 0 parental
females 46467304 (Acceptable) None

### Page 19 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

Developmental Toxicity in
Rabbits

0,5,15,30,45 mg/kg/day New Zealand

white rabbit Parental/

Developmental:

NOAEL= 30 mg/kg/day

LOAEL= 45 mg/kg/day based on mortality and clinical signs (decreased motor activity, head tilt, lacrimation, drooping eyelids,
diarrhea and salivation) for parental effects and
decreased fetal weight and urinary
tract malformations for developmental
effects

Mortality (6/25 rabbits) in 45 mg/kg/day group 46492903 (Acceptable) None

Terrestrial
Invertebrat

es Acute and

reproductive (28 days) Collembolan

(springtails) Species ( Folsomia candida) soil arthropods LC 50 >10 mg/kg

NOAEC (mortality) ≥ 10mg/kg

NOAEC (reproduction) = 1.8 mg/kg 45880404 (Supplemental) Non-guideline study

Growth and reproductive (8 weeks, adult 28 day exposure,
additional 4 week offspring exposure) Earthworms

( Eisenia fetida) LC 50 > 70.81 ug/kg

NOAEC ≥ 70.81 ug/kg (highest concentration tested)
No significant
treatment effects for mortality, behavior, body weights, reproduction or food consumption 45880402 (Supplemental) Non-guideline study

Triazole alanine (aquatic toxicity)

No submitted data identified

Triazole alanine (terrestrial toxicity)

### Page 20 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

Mammals 90-day oral

toxicity in
rodents – rat

0, 1250, 5000, 20000 ppm

M: 0, 90, 370, 1510 mg/kg/day

F: 0,160, 400, 1680 mg/kg/day Laboratory rat

(Rattus norvegicus) NOAEL = 90/160

mg/kg/day (M/F) LOAEL = 370/400 mg/kg/day (M/F)
based on decreased leukocyte counts and
decreased triglycerides in
females

At 1510/1680 mg/kg/day (M/F) decreased body weight (M), body weight gain (M), leukocytes (M/F) and triglycerides (M/F) 00164107 (Acceptable) None

Reproduction and fertility
effects 0, 200, 2000, 10000 ppm M: (F0/F1) 0, 50/47, 213/192, 1098/929 mg/kg/day F: 0, 51/49, 223/199, 1109/988 mg/kg/day Laboratory rat

(Rattus norvegicus) Parental:

NOAEC/NOAEL= 10000 ppm/929 mg/kg/day LOAEC/LOAEL:

>10000 ppm/929mg/kg/day

Offspring: NOAEC/NOAEL <250 ppm/19 mg/kg/day LOAEC/LOAEL=2000p pm/192 mg/kg/day
based on reduced mean litter weights in both generations
Reproduction: LOAEC/LOAEL>10000 ppm/929mg/kg/day 00164112 (Acceptable) None

Triazole acetic acid (aquatic toxicity)

Freshwater
Fish Acute Rainbow trout
( Oncorhynchus mykiss ) 96 hr-LC 50 >101 mg

ai/L
NOAEC = 101 mg ai/L
(mortality/sub-lethal effects) 48453209 (Acceptable) None

Freshwater
Invertebrat

es Acute Water flea ( Daphnia magna) 48-hr EC 50 > 108 mg

ai/L NOAEC = 108 mg ai/L 48453208 (Acceptable) None

### Page 21 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments (based on mobility, highest concentration tested)

Triazole acetic acid (terrestrial toxicity)

Mammals Acute Laboratory rat
(Rattus norvegicus) LD 50 > 5000 mg/kg 45596802 Review not available 2

14 day oral toxicity in
rodents

0, 100, 1000, 8000 ppm

M: 0, 10.6, 102.8, 788.3 mg/kg/day

F: 0, 10.1, 97.2,

703.5 mg/kg/day Laboratory rat

(Rattus norvegicus) NOAEL = 788.3/703.5

mg/kg/day
(M/F)
LOAEL >788.3/>703.5 mg/kg/day (M/F) 45596801 None

1 Many endpoints derived from summary document USEPA 2006 b. 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Human Health Aggrega te Risk Assessment in Support of Reregistration and Registration Actions for Triazol e-derivative Fungicide Compounds.

2 Values taken from triazole aggregate study reference d above, where it was noted that some values were from submitted summary data and full st udy reports were not available.



### Exposure Pathways of Concern

The exposure pathways for myclobutanil and its tran sformation products may result in a wide range of potential aquatic and terrestrial exposure scenarios. For this problem formulation, the drinking water and inhalation pathways for birds an d mammals were screened using the SIP (Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening methods. STIR found the inhalation pathway not likely to be significant but the SIP analysis identified exposure through drinking water alone to be a poten tial concern for birds (acute and chronic) and mammals (chronic only). This is primarily due t o the high water solubility of the compound and is a route of exposure that will be further ana lyzed in the forthcoming risk assessment.

It is also noted that these screening analyses do n ot include aggregation with all other exposure pathways (dietary, dermal, inhalation, or drinking water), which, together, may contribute to a total exposure that has a potential for effects to non-target animals. The risk characterization section will discusses the impact of the considerat ion of other routes of exposure that have

### Page 22 of 62

been identified as potentially important, and the d egree of certainty associated with screeninglevel risk assessment conclusions. SIP and STIR are described in detail at http://www.epa.gov/oppefed1/models/terrestrial/inde x.htm and the SIP and STIR model inputs and outputs for myclobutanil are available in Appendices B and C , respectively.

3. ANALYSIS PLAN

Drinking Water Assessment

An updated drinking water assessment will be conduc ted to support future human health dietary risk assessments of myclobutanil, as well a s an updated aggregate drinking water assessment for triazole-derivative fungicides. Such an assessment is needed because the fate half-lives calculated for this problem formulation in accordance with recent guidance (USEPA 2012 c.,d.) are likely to alter drinking water expo sure estimates. The drinking water assessment will incorporate model estimates of myclobutanil an d any additional transformation products to those previously identified by the Health Effects D ivision as residues of toxicological concern in surface water and groundwater. The registration rev iew drinking water assessment will include modeling results as well as a summary of available surface water and groundwater monitoring data, if available.

The current model for conducting drinking water ass essments for surface water is the Surface Water Concentration Calculator (SWCC). In the absen ce of newer models approved within OPP, it is expected that SWCC will be used to simulate p esticide transport as a result of runoff and erosion from an agricultural field and to estimate environmental fate and transport of pesticides in the index reservoir. Measures of exposure will b e based on maximum single and year (including multiple seasons per year) labeled appli cation rates, minimum retreatment intervals, and conservative methods of application.

Currently, groundwater modeling is completed using PRZM-Groundwater (PRZM-GW). PRZMGW is used to simulate vertical pesticide transport through the soil profile into an aquifer following application to an agricultural field. The PRZM scenarios used in groundwater simulations are representative of vulnerable sites— shallow unconfined aquifers under an agricultural field with leaching prone soil—and out put values represent pesticide concentrations that may be observed in drinking water resulting fr om the use of groundwater vulnerable to pesticide contamination as source water. The result s are expected to represent the upper bound
values on the concentrations of toxic residues that might be found in drinking water supplied by groundwater.

Ecological Risk Assessment

Stressors of Concern

Toxicity data for the primary degradate of concern 1,2,4-triazole as well as its conjugates (1,2,4- triazole alanine and 1,2,4-triazole acetic acid) ar e presented in Table 6 . Only the 1,2,4-triazole degradate was considered a major degradate based on soil and water metabolism studies for myclobutanil; however, 1,2,4-triazole acetic acid w as a major degradate in fate studies conducted for 1,2,4-triazole, and there is evidence that 1,2,4-triazole and the triazole conjugates can interconvert in soil and aquatic systems. (USEP A, 2006 a.). In addition to environmental

### Page 23 of 62

degradates of concern, plant and mammalian metaboli tes of concern of myclobutanil include 1,2,4-triazole, 1,2,4-triazole alanine, 1,2,4-triaz ole acetic acid and RH-9090 [α-(3-hydroxybutyl)- α-(4-chlorophenyl)-1 H -1,2,4-triazole-1-propanenitrile]. In addition to 1 ,2,4-triazole acetic acid, hydroxytriazole was identified as a major transform ation product of 1,2,4-triazole. Based on myclobutanil’s persistence in soil and water, it is considered unlikely that hydroxytriazole will reach levels greater than 10% of the parent compoun d in the environment. No toxicity data were available for hydroxytriazole.

Based on review of toxicity studies available for 1 ,2,4-triazole, 1,2,4- triazole alanine and 1,2,4- triazole acetic acid, these degradates appear to ge nerally show similar or less toxicity to aquatic or terrestrial organisms than the parent compound, myclobutanil. In general, aquatic species appear to be less sensitive to the degradates, wher eas birds and mammals tend to show similar toxicity. Previous documents (USEPA, 2006 b., Duah, et al. 2001) referenced an oral rabbit study
with an LD 50 

### of 666 mg/kg/day for 1,2,4-triazole but the study results could not be substantiated with the available literature (MRID cited did not c ontain an oral rabbit study). There has been some concern raised in other discussions (USEPA 200 6 b., Duah, et al. 2001) about the possible increased sensitivity of rabbits to the triazole de gradates based on the reported oral LD 50 

### of 666 mg/kg/day and mortality seen at 45 mg/kg/day in the neurodevelopmental study (MRID 46492903).

Although no toxicity studies are available for the metabolite RH-9090, this compound is considered to be of equivalent toxicity to the pare nt based on the structural activity relationship (SAR) (USEPA, 2006 b.). In addition, tolerances for myclobutanil residues in food are established for the combined residues of myclobutanil and RH-90 90 on registered commodities. For the degradates of concern, ECOSAR (Ecological Structure Activity Relationship), v1.11, and SMILES Codes were used to assess their toxicity relative t o the parent compound myclobutanil and aquatic organisms. Predicted values from ECOSAR for the parent compound myclobutanil were generally in agreement with the toxicity study resu lts, indicating ECOSAR may be useful for estimating degradate toxicity. The ECOSAR analysis indicated lower predicted toxicity for each of the degradation products than the parent, including the degradate hydroxytriazole, for which no toxicity data were available. Results of this analy sis as well as a summary table comparing toxicity study endpoints for myclobutanil and its d egradates are included in Appendix D

.

Previous assessments have used a Total Toxic Residu e (TTR) approach for assessing ecological and drinking water risks for myclobutanil and resid ues of concern in the absence of empirical toxicity data for the degradates. This modeling str ategy uses the assumption that all residues of concern have similar physical, chemical, and partit ioning characteristics as well as equal or less toxicity than the parent compound. Based on the re view of the toxicity studies available on the degradation products and ECOSAR analysis, it is ant icipated that the TTR approach will not be necessary for the aquatic ecological assessment and only the parent compound will be considered due to the lower toxicity of the degrada tes compared to the parent. However, as myclobutanil and its transformation products of con cern have generally equivalent toxicity for birds and mammals, degradates would be considered a s part of the terrestrial assessment for these species by using a conservative foliar half-l ife for the terrestrial analysis.

Measures of Exposure

### Page 24 of 62

In order to estimate risks of myclobutanil exposure to aquatic and terrestrial organisms, all exposure modeling and resulting risk conclusions wi ll be made based on maximum application rates, application methods, and any mitigation meas ures specifically indicated on the label. The models that will be used to predict the estimated e nvironmental concentrations (EECs) of myclobutanil are discussed on OPP’s model website http://www.epa.gov/opp00001/science/models_pg.htm . In addition, E-FAST and any additional available exposure models may be used to assess use in drains, drain lines, irrigation supply
systems, waste water systems, sewage systems, sewer lines, and storm sewers. E-FAST is
described in detail at http://www.epa.gov/oppt/exposure/pubs/efast.htm

.

The registration review preliminary risk assessment may include modeling exposures for some crops to account for the multiple crop cycles or cr op rotations that may occur within a given calendar year which may not have been previously co nsidered.

The Agency is also aware of monitoring conducted by federal and state agencies and this route of exposure will be considered in the assessment to the extent that data on myclobutanil and 1,2,4-triazole are available.

Measure of Effects

Ecological effects data are used as measures of dir ect and indirect effects to biological receptors. Data are typically obtained from registr ant-submitted studies and from literature studies identified by ECOTOX. The ECOTOX database p rovides more ecological effects data in an attempt to bridge existing data gaps. ECOTOX is a s ource for locating single chemical toxicity data and potential chemical mixture toxicity data f or aquatic life, terrestrial plants, and wildlife. ECOTOX was created and is maintained by t he U.S. EPA, Office of Research and Development, and the National Health and Environmen tal Effects Research Laboratory's MidContinent Ecology Division. Deficiencies were ident ified in the available toxicology data submitted to date from the registrant, including da ta gaps based on new guidelines or concern about species sensitivities. These are outlined in Tables 11 and 12 below.

Integration of Exposure and Effects

Risk characterization is the integration of exposur e and ecological effects to determine the potential ecological risk from the use of pesticide s and the likelihood of direct and indirect effects to non-target organisms in aquatic and terr estrial habitats. For the assessment of risks, the risk quotient (RQ) method is used to compare ex posure and measured toxicity values. EECs
are calculated for acute and chronic concentrations and are compared to acute and chronic toxicity endpoints. The resulting RQs are then comp ared to the Agency’s Levels of Concern (LOCs) (USEPA 2004). These criteria will be used to indicate when myclobutanil use, as directed on the label, has the potential to cause adverse di rect effects to non-target organisms. In addition, any available incident data will be consi dered (see below) as part of the risk
characterization.

Endangered Species Assessments

In November 2013, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS) (collectively, the Services), and the U.S. Department of

### Page 25 of 62

Agriculture (USDA) released a summary of their join t Interim Approaches for assessing risks to listed species from pesticides. The Interim Approac hes were developed jointly by the agencies in response to the National Academy of Sciences’ (NAS) recommendations and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. The NAS report ou tlines recommendations on specific
scientific and technical issues related to the deve lopment of pesticide risk assessments that EPA
and the Services must conduct in connection with th eir obligations under the Endangered Species Act (ESA) and FIFRA. The joint Interim Appr oaches were released prior to a stakeholder workshop held on November 15, 2013. In addition, th e EPA presented the joint Interim Approaches at the December 2013 Pesticide Program D ialogue Committee (PPDC) and StateFIFRA Issues Research and Evaluation Group (SFIREG) meetings, and held a stakeholder workshop in April 2014, allowing additional opportu nities for stakeholders to comment on the Interim Approaches. As part of a phased, iterative process for developing the Interim Approaches, the agencies will also consider public comments on the Interim Approaches in connection with the development of upcoming Registr ation Review decisions. The details of the joint Interim Approaches are contained in the white paper “Interim Approaches for NationalLevel Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report,” da ted November 1, 2013.

Given that the agencies are continuing to develop a nd work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, the ecological risk as sessment supporting the proposed interim registration review decision for myclobutanil is no t expected to contain a complete ESA analysis. Once the agencies have fully vetted the scientific methods necessary to complete risk assessments for endangered and threatened (listed) species and their designated critical habitats, these methods will be applied to subseque nt analyses for myclobutanil as part of completing this registration review.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerou s studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinog enicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. The se studies include endpoints which may be susceptible to endocrine influence, including effec ts on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental a nd reproductive effects in different taxonomic groups. As part of registration review f or myclobutanil, EPA will review these data and select the most sensitive endpoints for relevan t risk assessment scenarios from the existing hazard database. However, as required by FFDCA sec tion 408(p), myclobutanil is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether cer tain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or oth er such endocrine effects as the Administrator may designate.” The EDSP employs a t wo-tiered approach to making the statutorily required determinations. Tier 1 consist s of a battery of 11 screening assays to identify

### Page 26 of 62

the potential of a chemical substance to interact w ith the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal syst ems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any ad verse endocrine-related effects caused by the substance, and establish a dose-response relationsh ip between the dose and the E, A, or T
effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 [1] and includes some pesticides scheduled for registration review and chemicals fou nd in water

. Neither of these lists should be construed as a list of known or likely endocrine di sruptors.

Myclobutanil is on List 1 for which EPA has receive d all the required Tier 1 assay data. The Agency is currently reviewing all of the assay data received for the appropriate List 1 chemicals and planning to make the conclusions of those revie ws available in early 2015. For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines, and the Tier 1 screenin g battery, please visit our website. [2]



### [1] See http://www.regulations.gov/#!documentDetail;D=EPA-H Q-OPPT-2009-0477-0074 for the
final second list of chemicals.

[2] http://www.epa.gov/endo/

Review of Incident Data

Three incident databases are available: 1) the Ecol ogical Incident Information System v. 2.1.1 (EIIS), maintained by EFED; 2) the Avian Incident M onitoring System (AIMS), maintained by the American Bird Conservancy; and, 3) the Incident Dat a System (IDS) maintained by OPP. These databases were searched on 11/12/14.

The Ecological Incident Information System (EIIS) d atabase was queried for incidents related to myclobutanil use. Four incidents were reported in the EIIS database, three with effects on terrestrial plants (two incidents with grapes and o ne with roses) and one on aquatic species (both fish and invertebrates). The two incidents w ith grapes occurred in California and the one with roses was reported in Maryland. The certainty index for the damage in all 3 incidents to plants was rated as possibly related to exposure to myclobutanil. The two incidents with grapes involved application of other pesticides as well as the myclobutanil. Therefore, it is not definitively known whether or not the effects were due to exposure to myclobutanil in these two incidents. Myclobutanil was the only pesticide applied to the rose bushes in the third plant reported incident. In the fourth incident involving aquatic species, the incident was rated as highly probable. However, one other pesticide was i nvolved in this incident; therefore, it is not definitely known whether or not the effects were du e to myclobutanil exposure.

Incident 1: On May 30, 1994, Rally 40W (myclobutani l), Pro Gibb (gibberellic acid), dimethogan 25 WP, Pro Kil Cryolite 96 (sodium fluoa luminate), Britz binder and Booster 42

### Page 27 of 62

Foliar Spray (polymeric polyhydroxy acids) were app lied by ground application to grape vines. Shortly after the last application, scarring of the berries, stunted vine growth, lack of berry size increase, dieback of fruit from total bunches and l imited cone growth with straggly branches were observed. No residue analysis was conducted. The California Commissioner’s report
indicated that mixtures of Pro-Gibb 4% and Pro-Kil Cryolite 96 may have caused some compatibility problems. No specific data on terres trial plants were found in the Agency files for any of the pesticides applied on this incident.

Incident 2: On June 2, 2000, it was reported that R ally 40W damaged 6 acres of Red Globe and Thompson’s grapes to the extent that they were unfit for sale. Burns and necrosis on bunches (Red Globe) and leaf burn (Thompson’s) were observed. Agri-MEK (abamectin) and AdWet were also applied, using a ground spray on the vineyard. No plant tissue or environmental samples were found in the Agency files for any of t he pesticides applied in this incident.

Incident 3: On June 16, 2003, Systhane (myclobutan il) was applied via a broadcast spray to rose bushes grown in greenhouses by local reside nts in Maryland. The total magnitude was
200 houses. Foliar necrosis and some defoliation w ere observed after exposure to Systhane. Damage varied from house to house and by rose varie ty. No plant tissue or environmental samples were collected for this incident.

Incident 4: On July 28, 2009, an investigator for t he Iowa Department of Natural Resources visited a grower who was concerned an air plane may have applied or may have allowed a pesticide application to drift into Flint Creek in Des Moines County, IA. The inspector observed dead and dying crayfish in the creek. Fre shwater bluegill were also found dead. The active ingredients chlorpyrifos and myclobutanil we re detected in bluegill tissue samples.

A query of the aggregate Incident System (IDS) on 1 1/12/2014 reported 29 incidents to plants (dates ranging from 1998-2012).

The Avian Incident Monitoring System (AIMS), a data base administered by the American Bird Conservancy, was queried for myclobutanil on 11/12/ 2014 and to date, there were no bird incidents reported.

The absence of documented incidents in these databa ses does not necessarily mean that such incidents did not occur. Mortality incidents must b e seen, reported, investigated, and submitted to the Agency in order to be recorded in the incide nt databases. In addition, incident reports for non-target organisms typically provide information only on mortality events and plant damage. Sublethal effects in organisms such as abnormal beh avior, reduced growth and/or impaired reproduction are rarely reported, except for phytot oxic effects in terrestrial plants.

Uncertainties

• As previously discussed, many of the labels do not specify the maximum number of applications that can be applied per year or cro p cycle and/or the number of crop cycles per year. Some labels are missing a sin gle maximum application rate. We request that in completing the Use Pattern Summa ry Table, the registrants provide this information.

### Page 28 of 62 4. PRELIMINARY IDENTIFICATION OF DATA GAPS

Environmental Fate

Table 10 identifies the environmental fate studies by MRID that offer data for each Part 158 data requirement, as well as study classifications and whether or not further data are anticipated to be needed in order to support risk a ssessment for the myclobutanil registration review. Although no additional fate and transport d ata are being requested for myclobutanil under registration review, the table indicates stud ies for which data voluntarily submitted by the registrant may assist in refining the assessment. N o additional data for 1,2,4-triazole or its conjugates are needed to conduct the myclobutanil d rinking water or ecological risk assessments under registration review.

Table 10. Submitted Environmental Fate Data for Myc lobutanil

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed? Additional Comments

835.2120 Hydrolysis 00141679 Acceptable No None

835.2240 Aqueous

photolysis 00164560

40641501
40319801
40528801 Acceptable in

combination No Not requesting data but any
additional studies submitted voluntarily would help refine the

assessment

835.2410 Soil photolysis 00164987
00164988 Acceptable in

combination No None

835.4100 Aerobic soil

metabolism 00141680

00164561 Individual study

acceptable No Not requesting data but any
additional studies submitted voluntarily would help refine the

assessment

835.4200 Anaerobic soil

metabolism 00141680

00164561 Individual study

acceptable No Not requesting data but any
additional studies submitted voluntarily would help refine the

assessment

835.4300 Aerobic aquatic

metabolism 47454401 Acceptable No None

835.4400 Anaerobic

aquatic
metabolism No data No Not requesting data but any
additional studies submitted voluntarily would help refine the

assessment

835.1230 Adsorption/

desorption 00141682 Supplemental No None

835.1410 Volatility

–

laboratory No data No Not triggered based on low vapor pressure (7.07X10 -9 

### torr at 25°C)

835.6100 Terrestrial field

dissipation 00164563

00164987 Acceptable No None

### Page 29 of 62

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed? Additional Comments

835.6200 Aquatic field

dissipation No data No Not triggered based on exposure aquatic toxicity profile.

850.1730 Fish

bioconcentration No data No Low K ow 

### indicates a low potential for bioaccumulation.

850.6100 Analytical

method in soil No data No All field dissipation studies were conducted prior to April 19, 1996; therefore, Environmental Chemistry Method (ECM) and Independent Laboratory Validation (ILV) data are not required. 850.6100 Analytical

method in water No data No

Ecological Effects

Tables 11 and 12 identify the ecological effects studies, as well a s study classifications, and whether or not further data are anticipated to be n eeded in order to support risk assessment for registration review. The rationale for the addition al data that EFED recommends be requested is presented within the tables.

### Page 30 of 62

Table11. Submitted Aquatic Ecological Effects Data for Myclobutanil

OCSPP
Guideline Data Requirement

Test Material Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.1010 Freshwater

invertebrate acute toxicity 00141678 Acceptable No None

850.1025
850.1035 Estuarine/s altwater

invertebrate acute toxicity

42747901 Supplemental No Controls did not meet the minimum shell growth requirement of 2 mm (1.4- 1.5 mm control shell growth reported) in the eastern oyster study (MRID 42747901). Based on a
review of data from other conazoles, mysid shrimp has predominantly been a more sensitive species than the eastern oyster and toxicity values were generally similar. As an acceptable mysid shrimp study is available, a new oyster study is not requested at this time.

42747902 Acceptable No See above

850.1075 Freshwater fish

acute toxicity

TGAI

00144285 Acceptable Yes Under Guideline 850.1400, a
96-hour LC 50 

### is required for the test species used in the freshwater early life stage study (fathead minnow). There is uncertainty with the
available freshwater fish acute toxicity endpoint being the most sensitive species.
Based on the most sensitive chronic fish study, it is recommended that the study be conducted using the
fathead minnow.

850.1075 Saltwater fish acute

toxicity 42747903 Acceptable No None

850.1300 Freshwater

invertebrate life cycle No data No NOAEC estimated using ACR for mysid shrimp acute and chronic toxicity data

### Page 31 of 62

OCSPP
Guideline Data Requirement

Test Material Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.1350 Estuarine/saltwater

invertebrates life cycle

47968901 Supplemental No Estimated EECs based on the label application rates and frequency are expected to exceed the upper limit of toxicity testing for this study.
In the absence of additional toxicity data at higher dose ranges, the NOAEC of 0.0856 mg a.i./L will be used. Although protective, this could have implications for future endangered species
assessments due to the
conservative nature of the endpoint and could lead to overly conservative risk assumptions.

850.1735 Benthic

invertebrates (acute) No data No Not triggered per 40 CFR Part
158 based on chemical
characteristics

850.1740 Benthic

invertebrates (chronic) No data No Not triggered per 40 CFR Part
158 based on chemical
characteristics–

850.1400 Freshwater fish

early-life stage

00164986/

40409201/

40480401 Acceptable No As per 40 CFR, if a different test species is used for the chronic (early-life stage) data requirement than the acute study, a 96 hour LC 50 

### must be provided. If the acute study (850.1075) is repeated with
the fathead minnow as previously discussed, this requirement is fulfilled and an additional chronic study is
not needed.

### Page 32 of 62

OCSPP
Guideline Data Requirement

Test Material Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.1400 Estuarine/ saltwater

fish early-life stage

No data No If data are provided as mentioned regarding the 850.1400/850.1075 studies,
NOAEC can be estimated using ACR for freshwater fish acute and chronic toxicity data in lieu of providing this study.

850.1500 Fish life cycle

No data No Study not needed if 850.1400 requirements for freshwater
and saltwater fish are
fulfilled.

850.4400 Aquatic plant

Toxicity Test Using Lemna spp.

TEP No data Yes No toxicity data are available for myclobutanil to address risks to vascular plants. Multiple incident reports have involved myclobutanil and plant species.

850.4500 Algal Toxicity

TEP 41984801 Acceptable Yes Guidance recommends testing on four of the most
sensitive nonvascular organisms whereas submitted data only includes one. Multiple incident reports have involved myclobutanil and plant species. 850.4550 Cyanobacteria

(Anabaena flosaquae) Toxicity

TEP No data Yes

Table 12. Submitted Terrestrial Ecological Effects Data for Myclobutanil

OCSPP
Guideline Data Requirement

Test Material Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.2100 Avian oral toxicity 00144286 Acceptable Yes

### Page 33 of 62

OCSPP
Guideline Data Requirement

Test Material Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

TGAI

No data for passerine Based on effects noted in the available toxicity data, and the potential for passerines to be more sensitive than the species previously tested, EFED recommends requesting a passerine study.

850.2200 Avian dietary

toxicity 0144288 Acceptable No None

850.2300 Avian reproduction 43087901 Supplemental No Estimated EECs based on the label application rates and frequency are expected to exceed the upper limit of toxicity testing for the avian reproduction study. In the
absence of additional toxicity data at higher dose ranges, the NOAEC of 256 mg a.i./kg diet will be used to estimate risks. Although protective, this could have implications for future endangered species
assessments due to the
conservative nature of the endpoint and could lead to overly conservative risk assumptions.

Non

guideline Avian inhalation
No data No Based on STIR analysis, risks through inhalation pathway are not expected.

81-1 Acute mammalian
oral LD 50 

### (rat) 00165239/

00141662 Acceptable No None

83-4 Mammalian Reproduction (rat) 00149581/

00143766 Acceptable No None

### Page 34 of 62

OCSPP
Guideline Data Requirement

Test Material Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.3020 Honey bee adult

acute contact toxicity 00144289 Acceptable No Tier 1 toxicity test.

850.3030 Honey bee toxicity

of residues on foliage None No This study is not triggered based on the reported endpoint in the honey bee adult acute contact study.

Non

guideline

OECD TG
213 Honey bee adult

acute oral toxicity

TGAI No data Yes Tier 1 toxicity test.

Non

guideline

OECD TG
237 Honey bee larvae

acute and chronic oral toxicity

TGAI No data Yes Tier 1 toxicity test.

Non

guideline Honey bee adult

chronic oral toxicity

TGAI No data Yes Tier 1 toxicity test.

Non

guideline

OECD
Guidance

75 Semi

- field testing

for pollinators

TEP No data Yes Tier 2 test contingent on
results of tier 1 tests and screening level residues.

Non

guideline Field trial of

residues in pollen
and nectar

TEP No data Yes Tier 2 test contingent on
results of tier 1 tests and screening level residues.

850.3040 Field testing for

pollinators

TEP No data Yes Tier 3 testing contingent on
results of earlier tiers of testing.

### Page 35 of 62

OCSPP
Guideline Data Requirement

Test Material Submitted

Studies (MRID) Study

Classifications Are data

needed for
risk
assessment? Comments

850.4100 Terrestrial plant

toxicity: Tier II seedling

emergence

TGAI No data Yes No toxicity data are available for myclobutanil
to address risks to terrestrial plants. Multiple incident reports have involved myclobutanil and plant species. 850.4150 Terrestrial plant

toxicity: Tier II vegetative vigor

TEP No data Yes

### Page 36 of 62

Additional justification for non-guideline data req uests:



### Study Title: Honeybee Acute Oral Toxicity, Adult Non-guideline Study, OECD 213 Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, pesticide residues ma y be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive. Therefore, potential acute effects to adult honeybees and other insect pollinators from o ral exposure to some pesticides could exist. Currently available toxicity studies do not address possible effects of oral exposure on adult terrestrial insect survival. Because of the potenti al for pollen and nectar to be contaminated with pesticide residues, and subsequently brought b ack to the hive, it is important to determine the acute oral toxicity of this compound to adult h oneybees and other insect pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honeybee as a surrogate test species . The guidances discusses Tier I laboratorybased acute oral toxicity studies of individual adu lt bees as a critical component of the screening-level risk assessment process for examini ng potential adverse effects from specific routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance . Additional guidance on the honeybee oral toxicity test design can be found in OECD Test Guid eline 213 ( http://www.oecdilibrary.org/docserver/download/9721301e.pdf?expire s=1423074617&id=id&accname=guest&c
hecksum=2F0764FCB4DCF01D32382952A2E995C3 ) Practical Utility of the Data

How will the data be used? The Tier 1 acute oral toxicity data on adult honeyb ees serve as a foundation for the screeninglevel assessment of potential risk non-target organ isms such as federally listed threatened or endangered and non-listed terrestrial invertebrate insects, including pollinators, from acute oral exposures to pesticides. The data will be used to reduce uncertainties associated with the risk
assessment for terrestrial invertebrates and will i mprove EPA’s understanding of the potential direct and indirect effects on a broad range of tax a. This study will also provide information with which to compare whether oral toxicity estimates di ffer from contact toxicity estimates
obtained from other Tier 1 studies. If acute oral e ffects data for adult honey bees are not available, risks to terrestrial insects from acute oral exposure will be assumed.

How could the data impact the Agency’s future decis ion-making? The data will inform the determination required und er FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect lis ted threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk, which will limit the flexibility of pesticide produ cts to comply with FIFRA and the ESA, and could
result in use restrictions.

### Page 37 of 62

Study Title: Honeybee Acute Oral Toxicity, Larvae Non-guideline Study, OECD 237 Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, pesticide residues ma y be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where developing larvae and pupae may be exposed. Therefore, potential adverse effect s to developing bees could result from exposure to pesticide residues. Available toxicity studies do not address possible effects on brood (larvae and pupae) survival/development. Beca use of the potential for pollen and nectar to be contaminated with pesticide residues, and sub sequently brought back to the hive, it is important to determine the acute toxicity of this c ompound to bee brood.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honeybee as a surrogate test species . The guidances discusses Tier I laboratorybased acute toxicity studies of individual honeybee larvae as a critical component of the screening-level risk assessment process for examini ng potential risks from specific routes of exposure. The guidance be found at: http://www2.epa.gov/pollinator-protection/pollinato rrisk-assessment-guidance . Additional guidance on larval honeybee toxicity t est design can be found in OECD Test Guideline 237 ( http://www.oecdilibrary.org/docserver/download/9713171e.pdf?expire s=1422485600&id=id&accname=guest&c
hecksum=D8E07C2B1DF77BF096C3B29F55BF86A7 ). In some cases, information pertaining to acute toxicity to honey bee larvae may be obtained with the chronic honey bee larval test thereby negating the need for separate acute and ch ronic larval toxicity tests. Practical Utility of the Data

How will the data be used? The Tier 1 acute toxicity data on honeybee larvae s erve as a foundation for the screening-level assessment of potential risk to non-target organism s including federally listed threatened or endangered and non-listed terrestrial invertebrates , including pollinators, and/or modify their designated critical habitat from acute exposures to pesticides. The data will be used to reduce
uncertainties associated with the risk assessment f or terrestrial invertebrates and will improve EPA’s understanding of the potential effects on ter restrial species and whether there is a differential sensitivity of larval bees relative to adult bees. If acute effects data for larvae are not available, risks to terrestrial insects from ac ute exposure will be assumed.

How could the data impact the Agency’s future decis ion-making? The data will inform the determination required und er FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect lis ted threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide produ cts to comply with FIFRA and the ESA, and could
result in use restrictions.

### Page 38 of 62

Study Title: Pollinator Chronic Oral Toxicity, Adu lt Non-guideline Study Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. With eusocial bees, pesticide residues ma y be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive. Therefore, potential chronic effects to adult honeybees and other pollinators from oral exposure to some pesticides could exist. Currently available toxicity studies do not address possible lethal and sublethal effects of chronic oral exposure on adult terrestrial inverteb rates and will assist in determining whether the sensitivity of adult bees differs from that of earlier life stages. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine the chron ic oral toxicity of this compound to adult honeybees and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honeybee as a surrogate test species . The guidances discusses Tier I laboratorybased chronic oral toxicity studies of individual a dult honeybees as a critical component of the screening-level risk assessment process for examini ng potential risks from specific routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance . Although study design elements for the chronic 10-day oral toxicity test with honey bees a re similar to the OECD TG 213 acute oral toxicity test ( http://www.oecdilibrary.org/docserver/download/9721301e.pdf?expire s=1422484908&id=id&accname=guest&c
hecksum=C38495D2A570AC2216CFB1F223D24AA7 ), EPA requests that the proposed protocol for this study be submitted for review and approval by EPA prior to initiating the test. Practical Utility of the Data

How will the data be used? The Tier 1 chronic toxicity data on adult bees serv e as a foundation for the screening-level assessment of potential risk to non-target organism s including federally listed threatened or endangered species and non-listed terrestrial inver tebrates, including pollinators, from chronic oral exposures to pesticides. The data will be use d to reduce uncertainties associated with the
risk assessment for terrestrial invertebrates and w ill improve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect pollinators and to determine wh ether adult toxicity differs substantially from other life stages evaluated in other Tier 1 tests. If chronic oral effects data for adults are not available, risks to terrestrial insects from chroni c exposure will be assumed.

How could the data impact the Agency’s future decis ion-making? The data will inform the determination required und er FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect lis ted threatened or endangered species and/or their designated critical habitat. Without these d ata, EPA may need to presume risk which will

### Page 39 of 62

limit the flexibility of pesticide products to comp ly with FIFRA and the ESA, and could result in

use restrictions.

Study Title: Pollinator Chronic Oral Toxicity, Lar vae Non-guideline Study Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. For eusocial bees, pesticide residues ma y be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where larvae and pupae may be exposed. Therefore, potential effects to develop ing bees could result from chronic exposure to pesticide residues. Available toxicity studies do not address possible chronic effects on brood (larvae and pupae) survival. Because of the potent ial for pollen and nectar to be contaminated with pesticide residues, and subsequently brought b ack to the hive, it is important to determine chronic larval/pupal toxicity and whether adult eme rgence is adversely affected. This study will provide information on whether honeybee larvae diff er in sensitivity from adult bees following chronic exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honeybee as a surrogate test species . The guidances discusses Tier I laboratorybased chronic toxicity studies of individual honeyb ee larvae as a critical component of the screening-level risk assessment process for examini ng potential risks from specific routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance. Additional information on larval honeybee toxicity repeat exposure test design can be found i n the OECD draft guidance ( http://www.oecd.org/env/ehs/testing/Draft_GD_honeyb ees_rep_exp_for_2nd_CR_25_Novem ber_2013.pdf ). Although study design elements for the chronic 21-day toxicity test with honey bee larvae have been drafted, EPA requires that the proposed protocol for this study be submitted for review and approval by EPA prior to i nitiating the test. Practical Utility of the Data
How will the data be used? The Tier 1 chronic toxicity data on bee larvae serv e as a foundation for the screening-level assessment of potential risk to non-target organism s including federally listed threatened or endangered and non-listed terrestrial invertebrates , including insect pollinators, from chronic exposures to pesticides. These data will be used t o reduce uncertainties associated with the
risk assessment for terrestrial invertebrates and w ill improve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect pollinators. These data will al so assist in determining whether early life stages of the bee differ in their sensitivity to pesticide s relative to adults. If chronic effects data for larvae are not available, risks to terrestrial inse cts from chronic exposure will be assumed.

How could the data impact the Agency’s future decis ion-making?

### Page 40 of 62

The data will inform the determination required und er FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect lis ted threatened or endangered species and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide produ cts to comply with FIFRA and the ESA, and could
result in use restrictions.

Study Title: Pollinator Tier II Semi-Field Toxicity Testing (tunnel/enclosure studies) Non-guideline Study, OECD 75 Rationale for Requiring the Data

Tier II studies are conditional on the outcome of t he screening-level assessment where acute and/or chronic risk levels of concern have been exc eeded for terrestrial invertebrates. Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. For eusocial bees, pesticide residues may be transf erred to pollen and/or nectar of treated plants and subsequently brought back to the hive an d may adversely affect developing brood (egg, larvae, and pupae) and adult bees. Screening -level (Tier 1) studies of individual bees do not address possible effects and/or exposure to pestici de residues at the colony-level. Because of the potential for pollen and nectar to be contamina ted with pesticide residues, and subsequently brought back to the hive, it is important to determ ine whether bee colonies may be negatively affected under relatively controlled exposure condi tions of a semi-field study. In addition to providing effects data, these studies can provide d ata on pesticide residues in pollen/nectar of treated plants.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance desc ribes the tiered testing process and can be

found at: http://www2.epa.gov/pollinator-protection/pollinato r-risk-assessment-guidance

. Additional information on honeybee colony studies u nder semi- field conditions can be found in the

OECD Guidance 75 http://www.oecd.org/officialdocuments/publicdisplay documentpdf/?cote=env/jm/mono%28

. Practical Utility of the Data

How will the data be used? Tier II colony-level data will be used to assess po tential risk to non-target organisms including

listed and non-listed terrestrial social invertebra te species and to determine whether effects observed in the screening-level (Tier I) laboratory -based studies of individual bees are evident in colony-level studies under semi-field conditions. The Tier II semi-field test of whole colonies is a relatively controlled study, i.e ., bees are confined to a specific area, that is de signed to represent potential field-level exposure and account for hive dynamics, which are not achievable from other pollinator studies. This study will be used to determine whether adverse effects to insect pollinators at the whole colony level, may result f or the use of pesticides and will help to refine risk estimates derived in the screening-level risk assessment for beneficial terrestrial

### Page 41 of 62

invertebrates. Measured residues in pollen/nectar can also be used to refine risk estimates

derived from model-based or default values in the s creening-level assessment.

How could the data impact the Agency’s future decis ion-making? The data will inform the determination required und er FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non-target species or is likely to adversely affect federally listed t hreatened or endangered species or their designated critical habitat. Without these data, E PA may need to presume risk which will limit the flexibility of pesticide products to comply wit h FIFRA and the ESA, and could result in significant use restrictions.

Tier II Semi-Field Toxicity Testing for Pollinators (Feeding Studies) Rationale for Requiring the Data For eusocial bees, pesticide residues may be transf erred to pollen and/or nectar of treated plants and subsequently brought back to the hive an d may adversely affect developing brood (egg, larvae, and pupae) and adult bees. Tier II fe eding studies are conditional on the outcome of the screening-level assessment where acu te and/or chronic risk levels of concern
have been exceeded for terrestrial invertebrates ba sed on Tier I studies of individual bees. Feeding studies utilize free foraging bee colonies that are “dosed” with specific quantities of test material and represent a means of ensuring exp osure to the test material through spiked pollen and/or sugar solutions fed to the colony whi le still allowing the bees to forage freely. Since bee colonies are not confined to enclosures, colonies can be exposed for longer duration periods without subjecting the bees to str ess that typically results from Tier II tunnel studies. Available toxicity studies of individual bees (Tier 1) conducted to support screeninglevel assessments do not address possible effects a nd/or exposure to pesticide residues at the colony-level. It is therefore important to det ermine whether bee colonies may be negatively affected where bees are free foraging an d have the option to collect/consume alternative forage items beyond the spiked food. Si nce multiple dose levels can be more readily tested, feeding studies can help to define dose-response relationships at the whole colony level.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance describes the tiered testing process and
can be found at: http://www2.epa.gov/pollinator-protection/pollinato r-risk-assessmentguidance . Additional information on honeybee colony studi es under semi-field conditions
can be found in the OECD Guidance 75 http://www.oecd.org/officialdocuments/publicdisplay documentpdf/?cote=env/jm/mono%28

. Practical Utility of the Data

How will the data be used? Tier II colony feeding data will be used to assess potential risk to non-target organisms including listed and non-listed terrestrial social invertebrate species. The colony feeding study is designed to represent potential field-leve l exposure and account for hive dynamics

### Page 42 of 62

using longer duration exposure periods than are pos sible in Tier II tunnel studies. This study will be used to determine whether potential adverse effects to insect pollinators at the whole colony level when bees are able to forage naturally beyond the spiked food. Results from the feeding study will help to refine the screening-lev el risk assessment for beneficial terrestrial
invertebrates that were based on Tier I studies on individual bees. Since feeding studies can help to define a dose-response relationship at the colony level, the studies can provide a means of determining exposure thresholds below whic h the likelihood of adverse effects on colonies may be low.

How could the data impact the Agency’s future decis ion-making? The Tier II colony-level data will be used to refin e screening-level risk estimates derived using Tier I laboratory-based data on individual bees. T he Tier II data will help to inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adver se effects to non-target species or is likely to adversely affect federally listed threatened or end angered species or their designated critical habitat. Without these data, EPA may need to presu me risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA , and could result in significant use

restrictions.

Field Testing for Pollinators
OCSPP Guideline 850.3040 Rationale for Requiring the Data

Tier III studies are conditional on the outcome of the screening-level assessment (Tier 1) where acute and/or chronic risk levels of concern h ave been exceeded for terrestrial
invertebrates and where Tier II studies either unde r semi-field tunnel conditions and/or feeding studies have indicated potential adverse ef fects at the colony level. Available toxicity studies from lower-tier studies do not address poss ible effects and/or exposure to pesticide residues at the colony-level under actual pesticide use conditions and where specific uncertainties regarding the likelihood of exposure and/or effects remain. Full-field studies also provide an opportunity to measure residues in pollen and nectar as well as various matrices (beebread, honey, wax) within the colony t o obtain a more realistic understanding of exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for terrestrial invertebrates using the honeybee as a s urrogate test species. The guidance discusses Tier I laboratory-based acute oral toxici ty studies of individual adult bees as a critical component of the screening-level risk assessment pr ocess for examining potential adverse effects from specific routes of exposure. The guid ance can be found at: http://www2.epa.gov/pollinator-protection/pollinato r-risk-assessment-guidance . Additional guidance on the honeybee oral toxicity test design can be found in OECD Test Guideline 213 http://www.oecd-ilibrary.org/environment/test-no-21 3-honeybees-acute-oral-toxicitytest_9789264070165-en

. Practical Utility of the Data

### Page 43 of 62

How will the data be used? Tier III colony-level data will be used to further characterize potential risk to non-target organisms including listed and non-listed terrestri al social invertebrate species and to refine screening-level risk estimates that were based on i ndividual bee responses. The semi-field test is a controlled study that is designed to repr esent potential field-level exposure under relatively controlled conditions and account for hi ve dynamics, which are not achievable from lower-tier pollinator studies. This study will be used to determine whether adverse effects to insect pollinators at the whole colony level, may r esult for the use of pesticides and will help to refine the screening-level risk estimates for be neficial terrestrial invertebrates. This study
will also be used to determine whether more refined (Tier 3) studies are needed to
characterize risk.

How could the data impact the Agency’s future decis ion-making? The data will inform the determination required und er FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect fed erally listed threatened or endangered species or their designated critical habitat. Without thes e data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

Study Title: Field Trial of Residues in Pollen and Nectar Non-guideline Study Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides residues in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to hive all life stages m ay be exposed. For some pesticides, the quantification of pollinator-relevant residues in t reated flowering plants is needed, since pollinators will be exposed to residues from either current or prior season applications (due to the potential for residues to accumulate in plants and trees). Residues in edible/transportableto-hive parts of treated trees and plants, includin g (where appropriate), but not limited to, guttation water, sap/resins, whole plant tissue ( e.g., leaves, stems), as well as blooming, pollenshedding, and nectar producing parts ( i.e. , flowers and, if present, extra-floral nectaries) of plants may inform the potential for risk. Studies should be designed to provide residue data for crops and application methods of concern.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for bees using the honeybee as a surrogate. This can b e found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance. Since residue studies are intended to provide exposure data in multiple matrices and under specif ic application conditions, EPA requests that the protocol is submitted for review and approval b y EPA prior to initiation of the study. Practical Utility of the Data

### Page 44 of 62

How will the data be used?

Measured residue data will be used to refine conser vative estimates of pesticide exposure and reduce uncertainties associated with the Tier I exp osure assessment by providing direct measurements of pesticide concentrations resulting from actual use settings. Measured residues may provide a more realistic understanding of expos ure through contact or ingestion with which to calculate risk quotients for individual bees as well as to characterize exposure to the colony. If measured residue data are not available, risk estim ates for terrestrial insects will be based on model generated or default values used to support t he screening-level assessment.

How could the data impact the Agency’s future decis ion-making? The data will inform the determination required und er FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non-target species or is likely to adversely affect federally listed t hreatened or endangered species or their designated critical habitat. Without these data, E PA will have to rely on conservative estimates of exposure which may limit the flexibility of pest icide products to comply with FIFRA and the ESA, and could result in use restrictions.

### Page 45 of 62

References

FAO 2000. Appendix 2. Parameters of pesticides that influence processes in the soil. In FAO Information Division Editorial Group (Ed.), Pestici de Disposal Series 8. Assessing Soil Contamination. A Reference Manual. Rome: Food & Agr iculture Organization of the United Nations (FAO). http://www.fao.org/docrep/003/x2570e /x2570e00.htm

Duah, F.K, Fisher, J.M., Halder, C.A., Hall, L.R., Hall, T.A., Kelley, I., Tolliver, M.K. and Van Goethem, D. L., 2001. An Overview of the Available Data on 1,2,4-Triazole [Cas No. 288-88-0], a degradate of the Azole Class of Fungicides, and its Relevance to the Risk Profile of Tebuconazole (FOLICUR TM 

### ). Bayer Corporation. February 27, 2001.

USEPA. 2006 a. 1,2,4-Triazole, Triazole Alanine, Tr iazole Acetic Acid: Drinking Water Assessment in Support of Reregistration and Registration Actio ns for Triazole-derivative Fungicide Compounds. D320682. Office of Pesticide Programs En vironmental Fate and Effects Division, Environmental Risk Branch 1. February 28, 2006.

USEPA. 2006 b. 1,2,4-Triazole, Triazole Alanine, Tr iazole Acetic Acid: Human Health Aggregate Risk Assessment in Support of Reregistration and Re gistration Actions for Triazole-derivative Fungicide Compounds. DP Number 322215. Office of Pe sticide Programs Health Effects Division
and Environmental Fate and Effects Division. Februa ry 7, 2006.

USEPA. 2012 a. Drinking Water Exposure Concentratio ns for Proposed New Myclobutanil Uses on Grass Grown for Seed, Grass Pastures, Rangeland, and Sod Farms. D403754. Office of Pesticide Programs Environmental Fate and Effects D ivision, Environmental Risk Branch 3. November 20, 2012.

USEPA. 2012 b. Development and Use of Percent Cropp ed Area and Percent Turf Area Adjustment Factors in Drinking Water Exposure Asses sments: 2012 Update. Office of Pesticide Programs Environmental Fate and Effects Division. M ay 16, 2012.

USEPA. 2012 c. NAFTA Guidance for Evaluating and Ca lculating Degradation Kinetics in Environmental Media. December 17, 2012. U.S. Envi ronmental Protection Agency, Office of Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA. 2012 d. Standard Operating Procedure for Us ing the NAFTA Guidance to Calculate Representative Half-life Values and Characterizing Pesticide Degradation. November 30, 2012. U.S. Environmental Protection Agency, Office of Pes ticide Programs, Environmental Fate and Effects Division. Arlington, VA.

USEPA 2014 a. Guidance for Assessing Pesticide Risk s to Bees. Office of Pesticide Programs. June 23, 2014. http://www.epa.gov/pesticides/science/efed/policy_g uidance/team_authors/terrestrial_biolog y_tech_team/GuidanceAssessingPesticideRisk2Bees.pdf

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USEPA 2014 b. Myclobutanil Label Use Information S ystem (LUIS) Report. Biological and Economic Analysis Division.

USEPA 2014 c. Myclobutanil Summary Level Usage Ana lysis (SLUA). Biological and Economic Analysis Division.

Vogel, J.R., M.S. Majewski, and P.D. Capel., 2008. Pesticides in Rain in Four Agricultural Watersheds in the United States. J. Env. Qual. 37: 1101-1115.Page47of62Appendix A. Myclobutanil Transformation ProductsTable A1. Myclobutanil, its Major Transformation Products, and 1,2,4-Triazole Conjugates of Toxicological Concern.Code Name/SynonymChemical NameChemical StructureStudy TypeMRIDMaximumFormation(% Applied) andDay ObservedDuring StudyFinal Formation*(% Applied)And Study LengthPARENTMyclobutanilIUPAC Name:2-(4-chlorophenyl)-2-(1H1,2,4-triazol-1-ylmethyl)hexanenitrileCAS Number:88671-89-0Molecular Weight:288.775299 g/molChemical Formula:C15H17ClN4SMILES:CCCCC(CN1C=NC=N1)(C#N)C2=CC=C(C=C2)ClParent structure shown for referenceMAJOR TRANSFORMATION PRODUCTS1,2,4-TriazoleIUPAC Name:4H-1,2,4-triazoleMolecular Weight:69.0653 g/molChemical Formula:C2H3N3SMILES:C1=NN=CN1Aqueous photolysis1645604031980149% (30)Aerobic soilmetabolism14168016456118% (150, 180)13% (367)Terrestrial fieldDissipation00164563001649870-3” 22.8%(80)3-6” 2.9% (363)6-12” 2.1% (363)0-3” 3.3% (363)3-6” 2.9% (363)6-12” 2.1% (363)0-3” 14.4% (47,160)3-6” 58.6% (421)0-3” 6.3% (639)3-6” not detected(639)Page48of62Code Name/SynonymChemical NameChemical StructureStudy TypeMRIDMaximumFormation(% Applied) andDay ObservedDuring StudyFinal Formation*(% Applied)And Study Length6-12” 4.2% (47)6-12” 5.4% (639)1,2,4-TRIAZOLE CONJUGATES OF TOXICOLOGICAL CONCERN1,2,4-TriazoleAlanineIUPAC Name:2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acidChemical Formula:C5H8N4O2Molecular Weight:156.143SMILES:NC(CN1C=NC=N1)C(O)=O1,2,4-Triazole Conjugates Not Identified or Not Detected inAvailable Fate Studies1,2,4-TriazoleAcetic AcidIUPAC Name:2-(1H-1,2,4-triazol-1-yl)acetic acidChemical Formula:C4H5N3O2Molecular Weight:127.038SMILES:c1ncn(n1)CC(=O)O*Maximum % of applied reported at study termination; amounts may have continued to increase with timeBoldindicates maximum % formation percentage of degradatePage49of62Table A2. 1,2,4-Triazole, its Major TransformationProducts, and its Conjugates of Toxicological Concern.Code Name/SynonymChemical NameChemical StructureStudy TypeMRIDMaximumFormation(% Applied) andDay ObservedDuring StudyFinal Formation*(% Applied)And Study LengthPARENT1,2,4-TriazoleIUPAC Name:4H-1,2,4-TriazoleMolecular Weight:69.0653 g/molChemical Formula:C2H3N3SMILES:C1=NN=CN1Parent Structure Shown for Reference1,2,4-TRIAZOLE CONJUGATES OF TOXICOLOGICAL CONCERN1,2,4-TriazoleAlanineIUPAC Name:2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acidChemical Formula:C5H8N4O2Molecular Weight:156.143SMILES:NC(CN1C=NC=N1)C(O)=Oanaerobic soilmetabolism459307013.4%(7 d post-flood,total system)1.4%(122 d post-flood,total system)1,2,4-TriazoleAcetic AcidIUPAC Name:2-(1H-1,2,4-triazol-1-yl)acetic acidaerobic soilmetabolism452972037.8% (98 d)3.2% (293 d)Page50of62Code Name/SynonymChemical NameChemical StructureStudy TypeMRIDMaximumFormation(% Applied) andDay ObservedDuring StudyFinal Formation*(% Applied)And Study LengthChemical Formula:C4H5N3O2Molecular Weight:127.038SMILES:c1ncn(n1)CC(=O)O18.0% (98 d)11.7% (293 d)45284038< 0.1% (12 d)< 0.1% (180 d)0.2% (180 d)0.2% (28 d)0.2% (180 d)452840326.93% (14 d)Not Detected(120 d)1.67 % (14 d)Not Detected(120 d)0.27% (30 d)Not Detected(120 d)anaerobic soilmetabolism4593070150.3% (122 d post-flood,total system)MAJOR NON-CONJUGATE TRANSFORMATION PRODUCTSHydroxytriazoleIUPAC Name:1H-1,2,3-triazol-1-olMolecular Weight:85.065Chemical Formula:C2H3N3OSMILES:On1nncc1aerobic soilmetabolism452840383.1% (61 d)0.2% (180 d)< 0.1 % (180 d)30.8% (12 d)0.6% (180 d)0.9% (60 d)0.7%(180 d)21.5% (12 d)452840321.03% (61 d)Not Detected(120 d)Not Detected2.61% (14 d)Not Detected(120 d)*Maximum % of applied reported at study termination; amounts may have continued to increase with timeBoldindicates maximum % formation percentage of degradatePage51of62Appendix B. SIP analysis inputs and resultsTable B1. InputsParameterValueChemical nameMyclobutanilSolubility (in water at 25oC; mg/L)142Mammalian LD50(mg/kg-bw)1360Mammalian test speciesotherBody weight (g) of "other" mammalian species20Mammalian NOAEL (mg/kg-bw)16Mammalian test specieslaboratory ratBody weight (g) of "other" mammalian speciesAvian LD50(mg/kg-bw)498Avian test speciesnorthern bobwhite quailBody weight (g) of "other" avian speciesMineau scaling factor1.15Mallard NOAEC (mg/kg-diet)1250Bobwhite quail NOAEC (mg/kg-diet)256NOAEC (mg/kg-diet) for other bird speciesBody weight (g) of other avian speciesNOAEC (mg/kg-diet) for 2nd other bird speciesBody weight (g) of 2nd other avian speciesEnter body weight of 'other' mammalianspecies forLD50.Page52of62Table B2. Mammalian ResultsParameterAcuteChronicUpper bound exposure (mg/kg-bw)24.424024.4240Adjusted toxicity value (mg/kg-bw)511.442012.3066Ratio of exposure to toxicity0.04781.9846Conclusion*Drinking water exposurealone is NOT a potentialconcern for mammalsExposure throughdrinking water alone is apotential concern formammalsTable B3. Avian ResultsParameterAcuteChronicUpper bound exposure (mg/kg-bw)115.0200115.0200Adjusted toxicity value (mg/kg-bw)358.773927.2124Ratio of exposure to acute toxicity0.32064.2268Conclusion*Exposure throughdrinking water alone is apotential concern forbirdsExposure throughdrinking water alone is apotential concern forbirds*Conclusion is for drinking water exposure alone.This does not combine all routes of exposure. Therefore, whenaggregated with other routes (i.e., diet, inhalation, dermal), pesticide exposure through drinking water may contribute toa total exposure that has potential for effects tonon-target animals.

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Appendix C. STIR analysis results



# Welcome to the EFED Screening Tool for Inhalation Risk
This tool is designed to provide the risk assessor with a rapid method for determining the potential significance of the inhalation exposure route to bi rds and mammals in a risk assessment.



# Input

Application and Chemical Information

Enter Chemical Name Myclobutanil
Enter Chemical Use Fungicide Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) ground Enter Chemical Molecular Weight (g/mole) 288.78 Enter Chemical Vapor Pressure (mmHg) 9.75E-06 Enter Application Rate (lb a.i./acre) 1.4

Toxicity Properties

Bird
Enter Lowest Bird Oral LD 50 (mg/kg bw) 498 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178
Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 1360

Enter Lowest Rat Inhalation LC 50 (mg/L) 2.07 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 0.35



# Output
Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 1.52E-01 Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.90E-02
Adjusted Inhalation LD 50 4.23E+00
Ratio of Vapor Dose to Adjusted Inhalation LD 50 4.51E-03 Exposure not Likely Significant Maximum Post-treatment Spray Inhalation Dose (mg/kg ) 1.48E-01 Ratio of Droplet Inhalation Dose to Adjusted Inhala tion LD 50 3.50E-02 Exposure not Likely Significant



### Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 1.52E-01

### Page 54 of 62

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.39E-02
Adjusted Inhalation LD 50 1.23E+02
Ratio of Vapor Dose to Adjusted Inhalation LD 50 1.94E-04 Exposure not Likely Significant Maximum Post-treatment Spray Inhalation Dose (mg/kg ) 1.86E-01 Ratio of Droplet Inhalation Dose to Adjusted Inhala tion LD 50 1.51E-03 Exposure not Likely Significant

### Page 55 of 62

Appendix D. Toxicity comparison for myclobutanil an d degradates

Table D1. Additional Toxicity Endpoints for Myclobu tanil Degradates (1,2,4-triazole, triazole alanine and triazole acetic acid) 1

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

1,2,4-triazole (aquatic toxicity)

Freshwater
fish Acute Rainbow

trout (Salma gairdneri) 96-hr LC 50 = 760

mg a.i./L 00133380/4528

4017 Under Review

Chronic (28 day growth toxicity test) Rainbow

trout ( Oncorhynchu s mykiss ) LC 50 : > 100 mg/L

NOAEC (growth) ≥ 100 mg/L
NOAEC (sublethal effects) = 3.2 mg/L
LOAEC (sublethal effects) = 10.0 mg/L

Observed
sublethal effects included multiple fish being inactive or displaying abnormally low activity, labored respiration, and lying inactive on
the bottom of the aquarium in the three highest

concentrations
tested between days 23 and

28. 45880405

(Supplemental) Supplemental due to

non-guideline study

Acute Rainbow

Trout ( Salmo gairdneri ) 96 hr-LC 50 = 498

mg ai/L

NOAEC = 378 mg ai/L
(mortality) 48474301

(Acceptable) None

### Page 56 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

Freshwater
Invertebrat

es Acute Water flea ( Daphnia

magna ) LC 50 = 900 (730 to

2200, 95% C.I.) mg/L. 00133381 Under Review

Acute Water flea

( Daphnia magna) 48-hr EC 50 > 98.1

mg ai/L

NOAEC = 98.1 mg ai/L (based on mobility, highest

concentration tested) 48453206

(Acceptable) None

Aquatic
Plants -

Non
vascular Acute Freshwater Algae ( Pseudokirch
neriella subcapitata, formerly
Selenastrum capricornutu

m ) 96-hr endpoints:

Biomass (most sensitive):

EC 50 = 14 mg ai/L

NOAEC = 3.1 mg ai/L
Cell Density:

EC 50 = 18 mg ai/L

NOAEC = 6.8 mg ai/L

Growth Rate:

EC 50 > 31 mg ai/L

NOAEC = 6.8 mg ai/L 45880401

(Acceptable) None

Acute Green algae ( Scenedesmu s subspicatus ) EC 50 = 6.3 (5.5 to

7.1, 95% C.I.) mg/L 00133382 Under Review

1,2,4-triazole (terrestrial toxicity)

Birds Acute Coturnix quail LD 50 >316 mg /kg

bw 45284015 Under Review

Acute Bobwhite

quail ( Colinus virginianus ) LD 50 = 770 mg /kg

bw 49380701 Under Review

Mammals Acute Laboratory

mouse (Mus musculus) LD 50 = 3650

mg/kg 45284001 Review not available 2

Acute Laboratory Rat (M) LD 50 = 1375

mg/kg 45284008 Reviews not
available 2

### Page 57 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments (Rattus norvegicus) LD 50 = 1648-3080

mg/kg 45284004,

45284001

Reproduction and fertility effects 0, 250, 500, 3000

ppm M: 15, 31, 189
mkd

F: 18, 36, 218 mkd Laboratory

rat (Rattus norvegicus) Parental

NOAEC/NOAEL <250 ppm/15 mg/kg/day
Parental LOAEC/LOAEL= 250 ppm/15 mg/kg/day based
on decrease in bodyweight, bodyweight gain and spleen weight.

Offspring NOAEC/NOAEL= <250 ppm/19 mg/kg/day Offspring LOAEC/LOAEL= 250 ppm/19 mg/kg/day based
on decrease in bodyweight, bodyweight gain, brain and spleen weights

Repro NOAEC/NOAEL= 250 ppm/15 mg/kg/day Repro LOAEC/LOAEL= 500 ppm/31 mg/kg/day based
on abnormal sperm and ↓ # of

CL in F 1 females
At 3000 ppm/218 mg/kg/day, reproductive failure (no viable offspring), ↑ CL in

F 0 parental
females 46467304

(Acceptable) None

### Page 58 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

Developmental Toxicity in Rabbits

0,5,15,30,45 mg/kg/day New Zealand

white rabbit Parental/develop

mental NOAEL= 30 mg/kg/day

Parental/develop
mental LOAEL= 45 mg/kg/day based on mortality and clinical signs (decreased motor activity, head tilt, lacrimation, drooping eyelids,
diarrhea and salivation) for parental effects
and decreased fetal weight and urinary tract
malformations for developmental
effects

Mortality (6/25 rabbits) in 45 mg/kg/day group 46492903

(Acceptable) None

Terrestrial
Invertebrat

es Acute and

reproductive (28 days) Collembolan

(springtails) Species ( Folsomia candida) soil arthropods LC 50 >10 mg/kg

NOAEC (mortality) ≥ 10mg/kg

NOAEC (reproduction) = 1.8 mg/kg 45880404

(Supplemental) Non-guideline study

Growth and reproductive (8 weeks, adult 28 day exposure,
additional 4 week offspring exposure) Earthworms

( Eisenia fetida) LC 50 > 70.81 ug/kg

NOAEC ≥ 70.81 ug/kg (highest

concentration tested)
No significant
treatment effects for mortality, behavior, body weights, reproduction or food consumption 45880402

(Supplemental) Non-guideline study

Triazole alanine (aquatic toxicity)

### Page 59 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments

No submitted data identified

Triazole alanine (terrestrial toxicity)

Mammals 90-day oral toxicity

in rodents – rat

0, 1250, 5000, 20000 ppm

M: 0, 90, 370, 1510 mg/kg/day

F: 0,160, 400, 1680 mg/kg/day Laboratory

rat (Rattus norvegicus) NOAEL = 90/160

mg/kg/day (M/F) LOAEL = 370/400 mg/kg/day (M/F)
based on
decreased leukocyte counts
and decreased triglycerides in
females

At 1510/1680 mg/kg/day (M/F) decreased body weight (M), body weight gain (M), leukocytes (M/F) and triglycerides (M/F) 00164107

(Acceptable) None

Reproduction and fertility effects 0, 200, 2000, 10000 ppm M: (F0/F1) 0, 50/47, 213/192, 1098/929 mg/kg/day F: 0, 51/49, 223/199, 1109/988 mg/kg/day Laboratory

rat (Rattus norvegicus) Parental

NOAEC/NOAEL= 10000 ppm/929 mg/kg/day
Parental LOAEC/LOAEL:

>10000 ppm/929mg/kg/d

ay

Offspring NOAEC/NOAEL <250 ppm/19 mg/kg/day Offspring LOAEC/LOAEL=20 00ppm/192 mg/kg/day based
on reduced mean litter weights in both generations

Repro LOAEC/LOAEL>10

000 00164112

(Acceptable) None

### Page 60 of 62

Taxonomic Group Study type Surrogate Species Toxicity MRID (classification) Comments ppm/929mg/kg/d

ay

Triazole acetic acid (aquatic toxicity)

Freshwater
Fish Acute Rainbow

trout ( Oncorhynchu s mykiss ) 96 hr-LC 50 >101

mg ai/L

NOAEC = 101 mg ai/L
(mortality/sublethal effects) 48453209

(Acceptable) None

Freshwater
Invertebrat

es Acute Water flea ( Daphnia magna) 48-hr EC 50 > 108

mg ai/L

NOAEC = 108 mg ai/L (based on mobility, highest

concentration tested) 48453208

(Acceptable) None

Triazole acetic acid (terrestrial toxicity)

Mammals Acute Laboratory

rat (Rattus norvegicus) LD 50 > 5000

mg/kg 45596802 Review not available 2

14 day oral toxicity
in rodents

0, 100, 1000, 8000

ppm

M: 0, 10.6, 102.8, 788.3 mg/kg/day

F: 0, 10.1, 97.2, 703.5 mg/kg/day Laboratory

rat (Rattus norvegicus) NOAEL =

788.3/703.5 mg/kg/day
(M/F)

LOAEL >788.3/>703.5 mg/kg/day (M/F) 45596801 None

1 Many endpoints derived from summary document USEPA 2006 b. 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Human Health Aggrega te Risk Assessment in Support of Reregistration and Registration Actions for Triazol e-derivative Fungicide Compounds.

2 Values taken from triazole aggregate study reference d above, where it was noted that some values were from submitted summary data and full st udy reports were not available.

### Page 61 of 62

Table D2. Summary table of comparable toxicity data for myclobutanil and major degradate 1,2,4-triazole and its conjugates triazole alanine and triazole acetic acid 1



### Taxonomic group Study type Myclobutanil 1,2,4-triazole Triazole
Alanine Triazole

acetic acid

Freshwater fish Acute

96-hr LC 50 

### 2.4 mg/L

(Bluegill sunfish) 498 mg/L

(rainbow trout) >101 mg/L

Chronic NOAEC =0.98 mg/L

(fathead minnow) 3.2 mg/L

(rainbow trout) Estuarine/marine fish (sheepshead minnow) Acute

96-hr LC 50 

### 4.7 mg/L

Chronic

--

Freshwater
Invertebrates (water flea) Acute

48-hr EC 50 

### 11 mg/L > 98.1 mg/L >108 mg/L

Chronic NOAEC = 3.9 mg/L

(based on ACR analysis) Estuarine/marine
invertebrates (mysid shrimp) Acute

96-hr LC 50 

### 0.24 mg/L

Chronic NOAEC = 0.0856

mg/L (LOAEC > 0.0856 mg/L, no effects seen)
Aquatic Plants (Green algae) 120

- hr EC 50 

### 0.83 mg/L 6.3 mg/L

Birds (Bobwhite quail) Acute

LD 50 

### 498 mg/kg bw 770 mg/kg bw

Chronic NOAEC = 256 mg/kg

diet (LOAEC >256 mg/kg diet, no effects seen)

Mammals Acute

(mouse LD 50 

### ) 1360 mg/kg bw 3650 mg/kg bw > 5000 mg/kg bw

Acute (rat LD 50 

### ) 1600 mg/kg bw 1375 mg/kg bw

Chronic (rat NOAEL) 16 mg/kg bw 15 mg/kg bw 703.5 mg/kg bw 19 mg/kg

bw

1 

### See Tables 7-9 for individual study details.Page62of62Table D3. Comparison of ECOSAR outputs for myclobutanil and major degradate 1,2,4-triazole (and its conjugates triazole alanine and triazoleacetic acid) and hydroxytriazoleTaxonomic groupStudy type1MyclobutanilMyclobutanilMyclobutanil1,2,4-triazoleTriazoleAlanineTriazoleAcetic AcidHydroxytriazoleStudy Value(mg/L)ECOSAR Class:Benzyl Nitriles(mg/L)ECOSAR Class: Triazoles (Non-fused) (mg/L)Freshwater fish96-hr LC502.410.9333574.083.97 x 107*3.96 x 1057837.86Chronic ValueNOAEC = 0.981.730.1162.4655279.28169.424.637Estuarine/marinefish96-hr LC504.717.496.42314610.512.28 x 108*1.79 x 106*33075.76Chronic Value----0.1890.35063.3411.770.524FreshwaterInvertebrates96-hr LC50111109.949.7324526.292234.2684.61Chronic ValueNOAEC = 3.9(based on ACRanalysis)1.0590.96622.7753985.501611.6043.24Estuarine/marineinvertebrates96-hr LC500.241.0869.6121309.411.84 x 107*1.55 x 1052934.67Chronic ValueNOAEC = 0.0856(LOAEC > 0.0856,no effects seen)--14.9871260001.15 x 1011*4.99x 107*4.16 x 105Aquatic plants(green algae)96-hr LC500.832.5685.76279.461.09 x 105*4806.58143.48Chronic Value--1.5625.07459.00868398.533395.29104.85* = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by10X, typically no effects at saturation (NES) are reported.1Chronic values not available for some taxonomic groups